concanavalin-a and Mycobacterium-Infections

The production of interleukin-2 (IL-2) by Con A-activated spleen cells (SC) progressively declined and reached negligible values during the course of infection of C57BL/6 mice with Mycobacterium lepraemurium. In addition, the capacity of cultured SC to utilize IL-2 was highly reduced, as demonstrated by the accumulation of IL-2 activity in culture supernatants at 48 and 72 h after Con A activation. The depressed IL-2 utilization started to be observed about 1 to 2 weeks prior to the onset of the depressed IL-2 production and was not reversed by the addition of exogenous IL-2; thus implying that a lack of IL-2 utilization rather than a lack of IL-2 production could be directly responsible for the inhibition of T-cell proliferative responses to Con A in SC cultures of infected mice. The utilization of IL-2 was found to be down-regulated, at least in part, by splenic suppressor cells since, in mixed-culture experiments, SC from infected mice actively depressed the capacity of normal splenocytes to consume IL-2. Finally, the depressed IL-2 utilization would result from a 2- to 3-fold reduction of either or both the density of high-affinity IL-2 receptors and their affinity for IL-2.

Topics: Animals; Cells, Cultured; Concanavalin A; Female; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mycobacterium Infections; Mycobacterium lepraemurium; Receptors, Interleukin-2; Spleen; T-Lymphocytes

Mice were infected intravenously with 1.0 mg of Mycobacterium bovis BCG. At various times thereafter, spleen and peripheral lymph node cells were stimulated with concanavalin A for 18 to 20 h, and their capacity to produce interleukin-2 (IL-2) was evaluated by means of a T-cell blast proliferation technique. A depression of IL-2 production that was complete in the spleen but partial in lymph node cell cultures occurred at 2 to 3 weeks and persisted till weeks 8 to 10 after infection. No direct evidence was found for an active suppressor mechanism depressing in vitro the production of IL-2. In spleen cell cultures the suppression of IL-2 production would result from a functional defect of the IL-2-producing T-cell subset, whereas in lymph node cell cultures the depression mainly results from a relative lack of IL-2-producing cells caused by an accumulation of immunoglobulin-positive and "null" cells. Spleen cells from BCG-infected mice maintained their capacity to acquire IL-2 receptors when activated by concanavalin A.

Topics: Animals; B-Lymphocytes; Cells, Cultured; Concanavalin A; Female; Immune Tolerance; Interleukin-2; Leukocyte Count; Lymph Nodes; Lymphocyte Activation; Mice; Mycobacterium bovis; Mycobacterium Infections; Receptors, Immunologic; Receptors, Interleukin-2; Spleen; T-Lymphocytes; Time Factors

Different mouse strains were infected subcutaneously in the footpad with 10(7) Mycobacterium lepraemurium (MLM). At various stages of the infection, the number of acid-fast bacilli (AFB) in different organs, spleen cell interleukin 2 production, and specific IgM and IgG serum antibodies to MLM sonicate were assessed. Strains were separable into two distinct groups depending on the number of AFB recovered from the different organs, without any obvious influence of the Bcg gene. Thus C57BL/6, DBA/2, (C57BL/6 X DBA/2)F1 and C3H/Pas mice belonged to the high resistance group and DBA/1, BALB/c, and CBA strains to the low resistance group. Interleukin 2 production was depressed only in C57BL/6 and C3H/Pas mice. Anti-MLM antibody response also markedly varied according to strains, in terms of antibody titers, Ig class distribution, and species specificity, but with a different genetic pattern from that observed for MLM growth control.

Topics: Animals; Antibodies, Bacterial; Antibody Specificity; Concanavalin A; Dose-Response Relationship, Immunologic; Immunoglobulin G; Immunoglobulin M; Interleukin-2; Mice; Mice, Inbred Strains; Mycobacterium Infections; Mycobacterium lepraemurium; T-Lymphocytes

Groups of C57BL/6 mice were infected either intravenously or subcutaneously with 10(5) or 10(8) Mycobacterium lepraemurium cells, and the ability of their splenic macrophages and T-cells to produce, respectively, interleukin 1 on lipopolysaccharide stimulation and interleukin 2 on concanavalin A stimulation was assessed during the course of infection. In all groups of infected mice, interleukin 1 production remained unaffected during the entire observation period, whereas interleukin 2 activity decreased as the infection progressed. Heavily infected mice (10(8) M. lepraemurium cells) showed an earlier and stronger deficiency interleukin 2 production by concanavalin A-stimulated spleen cells than did mice infected with a lower dose (10(5) bacilli), without detectable influence by the route of inoculation. In mice receiving 10(5) bacilli, minor differences were seen according to the route of infection, with a slight delay in interleukin 2 decrease in mice injected intravenously. In subcutaneously inoculated mice, the failure of spleen cells to produce interleukin 2 after concanavalin A stimulation did not correlate with the number of bacilli developing in the spleen, suggesting the existence of suppressor mechanisms acting at a distance from the site of inoculation.

Topics: Animals; Concanavalin A; Female; Injections, Intravenous; Injections, Subcutaneous; Interleukin-1; Interleukin-2; Kinetics; Lipopolysaccharides; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mycobacterium Infections; Mycobacterium lepraemurium

Antigen-specific and mitogen-nonspecific T-lymphocyte proliferation and lymphokine release (interleukin 2 and macrophage activation factor) were studied in BALB/c and CBA mice infected intravenously with 10(8) Mycobacterium lepraemurium organisms. The responsiveness of spleen cells from infected animals to Con A and specific MLM antigen declined as the infection progressed. Thus, the decreased responsiveness appeared earlier and was more profound in the relatively susceptible BALB/c strain than in the relatively resistant CBA strain. Nylon-wool-purified, T-cell-enriched spleen cells from both strains, however, responded to both M. lepraemurium antigen and Con A until the later stages of infection (17 weeks postinfection). The relevance of nonspecific immunodepression mediated by nylon-wool-adherent spleen cells to the progressive nature of this infection is discussed.

Topics: Animals; Antigens, Bacterial; Concanavalin A; Female; Interleukin-2; Lymphocyte Activation; Lymphokines; Macrophage-Activating Factors; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mycobacterium Infections; Mycobacterium lepraemurium; Spleen; T-Lymphocytes

C57BL/6 and BALB/c mice were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At various times after infection, spleen cells were tested for their capacity to proliferate in vitro in response to concanavalin A (ConA) and to allogeneic cells. The generation of alloreactive cytotoxic T lymphocytes was also studied. The mitogen- and allogeneic-cell-induced blastogenesis of splenocytes from MLM-infected C57BL/6 and BALB/c mice was shown to be depressed during infection. The maximal decrease occurred 6 months after infection. Conversely, no reduction in the ability to generate alloreactive cytotoxic T lymphocytes was observed even after 6 months of infection. At the same time, interleukin 2 (IL2) activity generated by ConA stimulation of infected splenocytes was measured in both strains. IL2 activity in the ConA-stimulated culture supernatants was decreased as early as 1 month after MLM inoculation as compared with supernatants from age-matched control mice. Thus, IL2 production by infected-mouse spleen cells was shown to decline earlier than their proliferative responses to ConA and to allogeneic cells. ConA-induced T-cell blasts from infected mice showed a reduced ability to proliferate when incubated with an IL2-containing reference supernatant from ConA-stimulated normal spleen cells. These data suggest that a defect in IL2 production and utilization might contribute to the impairment of T cell-mediated immunity observed in MLM-infected mice.

Topics: Animals; Concanavalin A; Female; Interleukin-2; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mycobacterium Infections; Mycobacterium lepraemurium; Species Specificity; Spleen; T-Lymphocytes; T-Lymphocytes, Cytotoxic

Mice of the C57BL strain have been shown to be rather resistant to infection with Mycobacterium lepraemurium, whereas C3H mice are highly susceptible. Accordingly, it seemed to be somewhat paradoxical that enhanced antibody formation coupled with a depressed state of cell-mediated immunity as expressed by negative macrophage migration inhibition tests was observed not in C3H but in C57BL mice when they were inoculated with a large dose of murine leprosy bacilli, as reported in our previous studies. In the present study mitogen-induced DNA synthesis by lymph node cells was examined in 16 strains of mice which had been infected with a large or small dose of M. lepraemurium. According to the response to two kinds of T-cell mitogens, these mouse strains could be roughly divided into three groups consisting of two polar groups represented by C57BL/6J and C3H/HeN, respectively, and one intermediate between them. Furthermore, both humoral and cellular immune responses so far observed in C57BL and C3H mice were substantiated by DNA synthesis by lymph node cells harvested from these strains of mice and then exposed in vitro to B-cell and T-cell mitogens, respectively. However, no correlation was found between mitogen-stimulated DNA synthesis by these 16 strains of mice and their H-2 specificity.

Topics: Animals; Antibody Formation; Concanavalin A; DNA; Female; H-2 Antigens; Lipopolysaccharides; Lymph Nodes; Lymphocytes; Male; Mice; Mice, Inbred Strains; Mitogens; Mycobacterium Infections; Mycobacterium lepraemurium; Phytohemagglutinins; Species Specificity