concanavalin-a and Leprosy

The killing of Mycobacterium leprae by resting and gamma interferon (IFN-gamma)-activated macrophages in normal subjects and leprosy patients was assessed. Resting macrophages from normal individuals demonstrated the ability to kill M. leprae. For macrophages from tuberculoid patients, killing of M. leprae was only achieved in the presence of IFN-gamma, suggesting that initial T-cell activation occurs prior to the killing of M. leprae. In contrast, though activation with IFN-gamma rendered the lepromatous macrophages microbicidal, it failed to induce lymphocyte proliferation, suggesting a defect at either the antigen-presenting cell or the lymphocyte level or both. The concept that T-cell anergy is primarily due to lack of lymphokine generation was ruled out by our results, since responsiveness was restored in only a small proportion of lepromatous patients after exogenous lymphokine addition. In conclusion, this study demonstrated that killing and antigen presentation are two independent events. It appears that the ability of the macrophages per se to kill M. leprae may be of greater importance than lymphocyte-mediated activation for protection against M. leprae infection.

Topics: Animals; Antigen-Presenting Cells; Antigens, Bacterial; Blood Bactericidal Activity; Cell Communication; Concanavalin A; HLA-DR Antigens; Humans; Interferon-gamma; Leprosy; Leukocytes, Mononuclear; Lymphokines; Macrophage Activation; Macrophages; Mice; Mycobacterium leprae; Receptors, Fc; Superoxide Dismutase; T-Lymphocytes

The presence or absence of suppressor cells in leprosy patients was investigated by measuring peripheral blood lepromin-induced suppression of the Con A response. Significant suppressor activity was measured in 15 of 15 untreated or recently treated patients with lepromatous leprosy and 3 of 5 patients with borderline lepromatous leprosy. In addition, in patients with lepromatous leprosy, suppressor cell activity was found in 10 of 14 patients that had been under treatment for more than 1 year but in only 2 of 27 patients who had active or thalidomide controlled erythema nodosum leprosum. Suppression was observed in only 5 of 29 tuberculoid leprosy patients, 1 of 6 patient contacts, and 0 of 11 normal controls. The differences between the lepromatous or borderline lepromatous group as compared with the tuberculoid group were statistically significant (P less than 0.001). Our findings confirm the presence of lepromin-triggered suppressor cells in the peripheral blood of patients with lepromatous leprosy. These suppressor cells may contribute to the selective unresponsiveness of lepromatous patients to the antigens of Mycobacterium leprae.

Topics: Concanavalin A; Humans; Lepromin; Leprosy; T-Lymphocytes, Regulatory

The contribution of non-specific suppressor mechanisms to the overall immunoregulatory defect observed in lepromatous leprosy was evaluated. Con A-induced suppression was assayed using the standard two-stage test in 27 lepromatous leprosy patients, 19 of them during the quiescent stage (LL) and eight during erythema nodosum lepromatosum (ENL). Lymphocytes from normal individuals react in this assay, yielding higher suppression as the numbers of Con A-induced suppressor cells (Leu 2a+ cells) increase. In contrast, two patterns of response were observed in both LL and ENL patients: those giving lower suppression as the number of suppressor cells increased (LL-A and ENL-A) and those responding with the normal pattern (LL-B and ENL-B). The abnormal dose-response profile was not related to the disease stage, as both ENL and LL patients were included in groups with normal or atypical response. Reaction of the potential suppressor cells with anti-Leu 2a antibody abolished suppression in LL-B and normals, whereas Con A-induced suppression was unchanged or higher in ENL-A, ENL-B and LL-A, indicating that in these patients Leu 2a+ cells interfered with the generation of Con A-induced suppression. The contribution of spontaneous suppression was examined and it was shown that suppressor activity in the absence of Con A stimulus was higher in ENL (both ENL-A and ENL-B) and LL-A. Thus, it appears that the occurrence of high spontaneous suppressor activity, probably related to in vivo activation, is associated with a relative inability to generate de novo suppression after Con A stimulation in these patients.

Topics: Adult; Aged; Antibodies, Monoclonal; Concanavalin A; Erythema Nodosum; Female; Humans; Immune Tolerance; Leprosy; Male; Middle Aged; T-Lymphocytes, Regulatory

The extent to which M. leprae and its products induced suppression of T lymphocyte proliferation in vitro was evaluated. M. leprae antigens suppressed T cell proliferation in response to mitogens and antigens in both lepromatous and tuberculoid patients, as well as controls never exposed to M. leprae or M. leprae endemic areas. Both soluble and particulate fractions of M. leprae were found to suppress proliferation in a dose-dependent manner. The extent of suppression was inversely related to the proliferative response of the donors mononuclear cells to M. leprae. Evidence indicates that M. leprae contains both stimulatory and suppressive molecules for T cells. One such suppressive antigen, Lipoarabinomannan (LAM)-B of M. leprae, also suppressed the proliferative response of tuberculoid patients. Suppression was also observed with the LAM-B of M. tuberculosis. The suppressive effects observed were not due to the toxicity of the antigen. Some of the suppressive activity was mediated by T8+ suppressor cells and was expressed in both lepromatous and tuberculoid patients. We suggest that previous sensitization to M. leprae and other cross-reactive mycobacterial antigens determines the sensitivity of T cells to the suppressive effects of M. leprae antigens.

Topics: Antigens, Bacterial; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Concanavalin A; Humans; Immune Tolerance; Leprosy; Lipopolysaccharides; Lymphocyte Activation; Mycobacterium bovis; Mycobacterium leprae; Polysaccharides, Bacterial; T-Lymphocytes; Tuberculin

Although the mechanism of immunologic unresponsiveness in lepromatous leprosy remains unknown, it has been shown that interleukin-2 (IL-2) production is defective in these patients. Peripheral blood mononuclear cells (PBMC) were isolated from treated (less than 16 months) and untreated leprosy patients as well as household contacts; age, sex, ethnically matched control subjects; and laboratory staff. PBMC were cultured for 6 days with sonicated Mycobacterium leprae (1-10 micrograms/ml), Dharmendra lepromin (1:10), or phenolic glycolipid-I (PGL-I) (0.05-5.0 micrograms/ml) in medium supplemented with various concentrations of recombinant IL-2 (rIL-2) or cultured for 3 days with one of the three mycobacterial antigens in the presence of concanavalin A (ConA). TT/BT patients and household control subjects had a robust response to M. leprae and lepromin, but were unresponsive to PGL-I delivered in liposomes. PBMC from LL patients did not respond to any of the three antigen preparations. rIL-2 induced proliferation of PBMC both in leprosy patients and control subjects regardless of the presence or absence of the three leprosy antigen preparations. This antigen nonspecific augmentation of proliferation by the wide range of doses of rIL-2 employed makes difficult the interpretation of the enhanced thymidine incorporation noted when rIL-2 is added in the presence of antigen to cultures of lymphocytes from LL patients. Our studies are at variance with reports that leprosy antigens, specifically PGL-I, induce immunological suppression, in that mycobacterial antigens did not cause significant suppression of the ConA-induced proliferations of PBMC from patients.

Topics: Adolescent; Adult; Aged; Antigens, Bacterial; Cells, Cultured; Concanavalin A; Female; Glycolipids; Humans; Immune Tolerance; Interleukin-2; Lepromin; Leprosy; Lymphocyte Activation; Male; Middle Aged; Mycobacterium leprae; Recombinant Proteins

Using a costimulant assay, in vitro Con A responses of patients across the leprosy spectrum were found to be markedly suppressed by phenolic glycolipid-I (PGL-I), a unique antigen of M. leprae. The degree of inducible suppression as well as the number of leprosy patients showing suppression of mitogenic responses was higher with PGL-I as compared with integral M. leprae (p less than 0.05 to less than 0.01). Both untreated lepromatous (60%) as well as tuberculoid leprosy (67%) patients showed significant suppression ranging from 13 to 64% and 12 to 79%, respectively. Thus, PGL-I appears to have a universal suppressive effect on Con A responses and is unlikely to play a central role in determining the leprosy spectrum.

Topics: Antigens, Bacterial; Concanavalin A; Dose-Response Relationship, Immunologic; Glycolipids; Humans; Immune Tolerance; In Vitro Techniques; Leprosy; Lymphocyte Activation; Mycobacterium leprae

In lepromatous leprosy, there is extensive replication of Mycobacterium leprae (M. leprae) within dermal macrophages. This lack of microbial resistance has been attributed to a defective cell-mediated immune response to M. leprae antigens. We have examined the in vitro response of T cells to M. leprae to determine if hyporesponsiveness could be reversed. The study included 40 unselected patients from New York and from Colombia, most with the severe lepromatous form of the disease. We first noted that lepromatous leprosy patients were of two types: those unable to respond, as assessed by T cell proliferation and immune (gamma) interferon (IFN-gamma) release, and a second group, exhibiting low but detectable responses relative to tuberculoid controls. When the effect of exogenous recombinant interleukin-2 (IL-2) on the response to M. leprae antigens was compared in the two groups, many of the low responders, but not the nonresponders, showed enhanced proliferation and IFN-gamma release. To evaluate a possible suppressive effect of monocytes, these cells were eliminated with a cell-specific monoclonal antibody and complement. Depletion of monocytes often expanded preexisting weak responses but did not reverse the anergy of the M. leprae nonresponders. The enhancement was not M. leprae-specific, since it was also observed when bacillus Calmette-Guerin was the antigenic stimulus for proliferation and IFN-gamma production. Removal of the suppressor T cell subset, with OKT8 antibody and complement, also did not restore responses in nonresponder patients. We conclude that a sizable number of lepromatous leprosy patients exhibit a low degree of responsiveness to M. leprae and that the responses can be enhanced in vitro with IL-2 or with monocyte depletion. Nonresponsiveness, however, cannot be reversed. Since currently available assays measure the function of previously sensitized T cells, suppressor mechanisms may yet contribute to defective cell-mediated immunity by impairing the initial sensitization to M. leprae antigens.

Topics: Adult; Antigens, Bacterial; Child; Concanavalin A; Female; Humans; Immunity, Cellular; Interferon-gamma; Interleukin-2; Leprosy; Lymphocyte Activation; Male; Middle Aged; Mycobacterium bovis; Mycobacterium leprae; T-Lymphocytes

Human peripheral blood mononuclear cell proliferation induced by Mycobacterium leprae could be inhibited by the suppressor factor in the lysate of the macrophages of lepromatous leprosy patients. Macrophages from normal subjects and tuberculoid patients did not show production of a suppressor factor. Inhibition occurred only when the factor was present in the initial stages of lymphocyte culture. The factor is heat stable and nondialyzable. Proliferation induced by some mycobacteria and concanavalin A could also be blocked by the factor. Interestingly, blastogenic response by a few other antigens and phytohemagglutinin could not be inhibited by the suppressor factor. Mononuclear cells pretreated with such lysate from lepromatous macrophages for 24 h could induce suppressive activity in the cells in vitro in an autologous system. Treatment of these cells with carbonyl iron after the induction phase, to remove phagocytic cells, did not abolish their suppressive activity. The lepromatous macrophage lysate also generated suppressive activity in a T-lymphocyte-enriched population of normal subjects. These studies are interpreted to indicate that immunosuppression in lepromatous patients is produced by both macrophages and T lymphocytes. The exact phase in which either of these cells acts as a suppressor may be different. Specific suppression by macrophages to M. leprae can be an early event, and nonspecific suppression by T lymphocytes may be a later event in the course of lepromatous leprosy.

Topics: Concanavalin A; Humans; Immune Tolerance; Leprosy; Lymphocyte Activation; Lymphokines; Macrophage Migration-Inhibitory Factors; Macrophages; Mycobacterium; Mycobacterium leprae; Suppressor Factors, Immunologic; T-Lymphocytes; T-Lymphocytes, Regulatory; Time Factors

Topics: Concanavalin A; Disease Susceptibility; Humans; Immunity, Cellular; Immunoglobulins; Leprosy; Lymphocyte Activation; T-Lymphocytes, Regulatory

ConA-induced suppressor activity in patients with lepromatous leprosy (LL) was studied. Patients were studied during and after erythema nodosum leprosum (ENL) reactions. The study included 16 patients with ENL, nine of whom returned once the ENL episode was over. Patients were compared to 12 normal controls. Suppressor activity was evaluated in vitro by cultivating peripheral blood lymphocytes (PBL) with an inducer of T suppressor cells, concanavalin A (ConA), and with two different mitogens, phytohemagglutinin (PHA) and ConA, in order to measure the inhibition of the proliferative responses in all cases. In contrast, in LL patients during ENL the ConA-induced suppressor response was markedly reduced. The reduction in suppressor responses was even more marked in the LL patients after the ENL episode. Reduced levels of suppressor activity in LL patients reveal a defect in central mechanisms of control in the immune response.

Topics: Adult; Concanavalin A; Erythema Nodosum; Female; Humans; Leprosy; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Regulatory

Previous studies from this laboratory have suggested a role for cell-mediated immunity in host defense against Legionella pneumophila. In this paper, cell-mediated immunity to L. pneumophila in patients recovered from Legionnaires' disease was studied by examining patient mononuclear cell responses to L. pneumophila antigens. Patient mononuclear cells were assayed both for their capacity to respond to L. pneumophila antigens with the production of cytokines that activate monocytes, as measured by monocyte inhibition of L. pneumophila multiplication, and for their capacity to respond with proliferation, as measured by [(3)H]thymidine incorporation. Patient mononuclear cells incubated with formalin-killed L. pneumophila generated cytokines (supernatants) that were capable of activating in vitro freshly explanted monocytes from a person without historical or serological evidence of L. pneumophila infection (nonpatient). Such activated nonpatient monocytes inhibited the intracellular multiplication of L. pneumophila, and the degree of inhibition was proportional to the concentration of supernatant added. Patient mononuclear cells incubated with 5 x 10(6) - 5 x 10(8) formalin-killed L. pneumophila/ml for 4 d produced maximally potent supernatants; supernatants generated in flat-bottomed wells were equivalent in potency to supernatants generated in cone-shaped wells. Patient L. pneumophila-induced mononuclear cell supernatants were less potent than patient concanavalin A-induced mononuclear cell supernatants. Patient mononuclear cells also responded to formalin-killed L. pneumophila with proliferation (lymphoproliferation). Patient mononuclear cells responded more strongly to L. pneumophila antigens than mononuclear cells of age- and sex-matched nonpatients, as measured by both assays; responses to concanavalin A were comparable. Mononuclear cells from patients recovered from Legionnaires' disease responded more strongly to L. pneumophila than to Mycobacterium leprae antigens, whereas mononuclear cells from patients with tuberculoid leprosy responded more strongly to M. leprae antigens. These findings indicate that cell-mediated immunity to L. pneumophila develops in patients with Legionnaires' disease and, taken together with previously reported findings, that cell-mediated immunity plays a major role in host defense against L. pneumophila. The monocyte activation assay described in this paper has general applicability for the study of monocyte and mononuclear

Topics: Aged; Antigens, Bacterial; Biological Products; Cell Division; Cells, Cultured; Concanavalin A; Cytokines; Female; Humans; Immunity, Cellular; Legionella; Legionnaires' Disease; Leprosy; Lymphocytes; Male; Middle Aged; Monocytes; Mycobacterium leprae

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.

Topics: Antigens, Bacterial; Concanavalin A; Humans; Interferon-gamma; Leprosy; Monocytes; Mycobacterium leprae

Lymphocytes from peripheral blood were isolated from leprosy patients and healthy contacts (HC) of leprosy patients and stimulated in vitro with: Mycobacterium leprae and a M. leprae cell wall antigen, MLW 1; tuberculin purified protein derivative (PPD); antigens prepared from Candida albicans, Entamoeba histolytica, Leishmania aethiopica, and parotitis virus; the non-specific mitogens phytohemagglutinin (PHA) and concanavalin A (Con-A). Lymphocytes from patients with untreated lepromatous leprosy failed to respond to the M. leprae antigens, and the median response to PPD was also significantly (p less than 0.005) lower than in the HC group. They responded almost as well as the other groups to non-mycobacterial antigens, PHA, and Con-A. In LL patients who had been treated with dapsone for several (median 10) years, the failure to respond to M. leprae antigens remained, but the depression of the PPD response and the slight non-specific depression of the lymphocyte stimulation test (LST) responsiveness had been reversed. Our results confirm that the major defect in the cell-mediated immune response of LL patients is M. leprae-specific and permanent. The possibility that the defect may be due to a continuous, antigen-induced suppression of the immune response is discussed. That the defect also affected the response to PPD is important since it points to a clear antigenic relationship between M. leprae and BCG/M. tuberculosis. Evidence is presented suggesting that an antigen induced suppressor mechanism may be operating in vitro with cells from patients with borderline tuberculoid leprosy.

Topics: Adolescent; Adult; Aged; Antigens, Bacterial; Concanavalin A; Dapsone; Female; Humans; Immunity, Cellular; In Vitro Techniques; Leprosy; Lymphocyte Activation; Male; Middle Aged; Mycobacterium leprae; Phytohemagglutinins; Tuberculin; Tuberculosis

T cell subsets and T cell functions were explored in 31 leprosy patients with the following methods: determination of the percentages of the different T cell subpopulations defined by monoclonal antibodies directed at total T cells, helper T cells and suppressor/cytotoxic T cells; measurement of the in vitro proliferative responses to mitogens; study of the concanavalin A-induced suppressive activity, assessed on MLC; measurement of delayed-type hypersensitivity by skin testing. The confrontation between immunological lepromatous patients without type-2 reaction (erythema nodosum leprosum), (2) lepromatous patients without ENL (erythema nodosum leprosum), (2) lepromatous patients was recent ENL and (3) tuberculoid patients. Unexpectedly, groups 1 and 3, although differing strongly in their clinical status and their sensitivity to lepromin (absent in group 1 and strong in group 3), showed a similar immunological profile with a normal percentage of T cells and a normal distribution of T cells among the major T cell subset contrasting with a moderate decrease of proliferative responses to mitogens and impaired delayed-type hypersensitivity reactions. Concanavalin A-induced suppressive activity was type-2 reaction) strongly differed from both other groups, showing striking abnormalities other groups, showing striking abnormalities of the repartition of the T cell subsets, with increased percentages of helper T cells and decreased percentages of suppressor T cells, and elevated proliferative responses to mitogens. Concanavalin A-induced suppressive activity was reduced in most patients of this group. It is suggested that this imbalance between T cell subsets contributes to the occurrence of ENL reactions in lepromatous patients.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Concanavalin A; Female; Humans; Intradermal Tests; Leprosy; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes; T-Lymphocytes, Regulatory

The sera of ten Egyptian man with long-standing lepromatous leprosy (LL) (mean duration 17.4 years) that had failed to respond to dapsone treatment were shown to inhibit mitogen stimulation responses of normal human lymphocytes. When first tested, the sera partly inhibited the response to phytohaemagglutinin (PHA) and pokeweed mitogen and virtually abolished that to concanavalin A (Con A): after repeated freezing and thawing, the Con A inhibition had disappeared, whereas the PHA response was still partly inhibited. The inhibitory serum factor(s) had similar actions on lymphocytes from each of six normal donors. Although the sera varied in potency, they showed similar dose-response curves when tested against lymphocytes from a single donor. The principal action of the sera was to reduce the number of cells responding to mitogen, without modifying the kinetics of recruitment or rate of volume growth during G1-phase in those cells that were unaffected by the inhibitory substances(s). Study of PHA dose-response curves and of the effect of delayed addition of LL serum suggested that the serum factor(s) act by diminishing the responsiveness of the cells, rather than by reducing the concentrations of free mitogen or by blocking cell membrane mitogen receptors. The serum from one apparently healthy attendant, who had nursed leprosy patients for 30 years but who did not have leprosy or other chronic infective disease, inhibited completely stimulation by all three mitogens in a manner different from that of LL sera. Serum from the other 13 control patients did not modify the response of normal lymphocytes to stimulation by any of the three mitogens studied. It was concluded that the inhibitory factor(s) in the serum of patients with LL were a consequence of the disease and not of the environment in which the patients lived. Microscopy confirmed that the techniques used for recovery of the cultured cells did not introduce bias into the volume spectroscopy measurements.

Topics: Adult; Cell Count; Cell Cycle; Cells, Cultured; Concanavalin A; Dapsone; Humans; Leprosy; Lymphocyte Activation; Male; Middle Aged; Mitogens; Phytohemagglutinins; Pokeweed Mitogens

The effect of granulomatous infections upon the activity of a T lymphocyte subclass in human peripheral blood that can be induced by concanavalin A (Con A) to function in a suppressor mode was studied. Peripheral blood lymphocytes (PBL) from eleven patients with disseminated mycotic or mycobacterial infections or from controls were preincubated with and without Con A, washed and cultured with allogeneic PBL freshly drawn from healthy donors sensitive to histoplasmin. DNA synthesis was then measured in co-cultures stimulated by Con A, histoplasmin, or by the mixed lymphocyte culture (MLC) reaction alone. As compared with cells preincubated without Con A, the Con A-pretreated cells were significantly less effective in suppressing the responses of normal PBL to histoplasmin (P < 0.01), and in a one-way MLC reaction (P < 0.05). The Con A-induced suppressor activity of PBL from nine patients with localized granulomatous infections did not differ significantly from that exerted by PBL of normal controls in two of the three co-culture systems employed. These studies suggest that either dysfunction or a reduction of the Con A-inducible T-suppressor cell subpopulation in peripheral blood is frequent among patients was disseminated granulomatous infections.

Topics: Adolescent; Adult; Aged; Blastomycosis; Concanavalin A; Histoplasmin; Histoplasmosis; Humans; Hypersensitivity, Delayed; Leprosy; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Skin Tests; T-Lymphocytes, Regulatory; Tuberculosis

Six families with HLA-D-identical siblings suffering from leprosy were studied. Lymphocytes and macrophages isolated from the peripheral blood were co-cultured with allogeneic, HLA-D-identical cells and stimulated with M. leprae antigens and concanavalin A. Tuberculoid patients had circulating lymphocytes which showed marked functional suppression of lymphoproliferative responses to antigen and mitogen. In contrast, lepromatous patients showed weak lymphocyte suppressor activity. Macrophages derived from responder individuals augmented, while those derived from lepromatous patients inhibited, M. leprae-induced proliferation of lymphocytes.

Topics: Antigens, Bacterial; Concanavalin A; Histocompatibility Antigens Class II; Humans; Immunity, Cellular; Leprosy; Lymphocyte Activation; Macrophages; Mycobacterium leprae; T-Lymphocytes, Regulatory

Topics: Animals; Antilymphocyte Serum; Concanavalin A; Horses; Humans; Immunosuppression Therapy; Lepromin; Leprosy; Mycobacterium leprae; Sheep; T-Lymphocytes

Peripheral blood lymphocytes from sixty leprosy patients and eight healthy contacts known to be responsive to M. leprae, were stimulated in vitro with concanavalin A (Con A) or PPD alone or in combination with autoclaved, whole M. leprae. Time kinetics and the percentage of inhibition induced by M. leprae differed in the two disease groups and contacts. Antigen-generated suppression of Con A-stimulated lymphocyte transformation was observed on day 4 in seventeen of twenty-one (80%) tuberculoid patients and six of seventeen (35.3%) untreated lepromatous patients. Healthy contacts and 53% lepromatous individuals showed enhanced Con A responses in the presence of antigen. On prolongation of antigen presence to 6 days, a marginal effect was noted in the tuberculoid group. In contrast, all healthy individuals and some lepromatous patients showed increased inhibition of Con A responses. M. leprae antigens showed uniform inhibition of PPD-induced 3H-thymidine incorporation in leprosy patients and healthy contacts.

Topics: Antigens, Bacterial; Cells, Cultured; Concanavalin A; Humans; Immunosuppression Therapy; Leprosy; Lymphocyte Activation; Lymphocytes; Mycobacterium leprae; Time Factors; Tuberculin

The possibility of an active mechanism of immunologic suppression in leprosy was explored by assessing the in vitro lymphocyte responses of 61 leprosy patients and 30 normal individuals to the mitogen Con A in the presence or absence of Dharmendra lepromin. Lepromin-induced suppression of Con A stimulation was found in 32 of 35 lepromatous patients and 15 of 15 borderline patients, but only 2 of 15 tuberculoid patients and 2 of 30 normal controls. Cell fractionation studies indicated at least two cell populations involved in the in vitro lepromin-induced suppressor activity, adherent cells and T gamma-cells.

Topics: Cell Adhesion; Concanavalin A; Humans; Immunoglobulin G; Lepromin; Leprosy; Lymphocyte Activation; Lymphocytes; Receptors, Fc; Rosette Formation; T-Lymphocytes, Regulatory

Peripheral blood lymphocytes from nine normal subjects and 40 patients with leprosy were pretreated in vitro with Concanavalin A (Con A). Cells from normal subjects pretreated for 24 hours showed consistent and effective generation of suppressive activity which inhibited mitogen induced transformation of autologous lymphocytes. Prolongation of Con A pretreatment to 40 hours resulted in maximal suppressive activity. Tuberculoid leprosy patients had lymphocytes in their blood which on 24 hour pretreatment with Con A exerted suppressive effects markedly greater than the maximal suppression noted with 40 hour pretreated normal lymphocytes. In contrast, untreated patients with polar lepromatous leprosy showed a decrease in suppressive activity which could not be altered by prolongation of Con A pretreatment: the loss of suppressive activity noted in this form of leprosy was restored during erythema nodosum leprosum.

Topics: Concanavalin A; Erythema Nodosum; Humans; Leprosy; Lymphocyte Activation; Mitogens; Mitomycins; Mycobacterium Infections, Nontuberculous; Mycobacterium leprae; T-Lymphocytes, Regulatory