concanavalin-a and Lymphocytosis

A case of chronic lymphoproliferative disorder is presented, wherein a morphologically homogeneous population of lymphoid cells displayed properties similar to those described for large granular lymphocytes (LGL). Besides their LGL-like phenotype (VEP 13+, OKM 1+, OKT 10+ Fc-IgG-receptor+, OKT 3-), the proliferating cells were cytotoxic to NK targets as well as to antibody-coated target cells. Clinically, our patient presented low-grade lymphocytosis, splenomegaly, neutropenia, hyperimmunoglobulinemia and recurrent infections. Based upon this and 32 similar cases reported in the literature, we conclude that lympho-proliferative disorders involving GL encompass a variety of clinical entities, ranging from reactive GL lymphocytoses to overt lymphocytic malignancies.

Topics: Adult; Aged; Antibodies, Monoclonal; Bone Marrow; Concanavalin A; Female; Humans; Hypergammaglobulinemia; Isoantigens; Killer Cells, Natural; Leukemia; Lymphocyte Activation; Lymphocytes; Lymphocytosis; Male; Microscopy, Electron; Middle Aged; Neutropenia; Phenotype; Phytohemagglutinins; Receptors, Fc; Receptors, IgG

Viruses are believed to contribute to the pathogenesis of autoimmune type 1A diabetes in humans. This pathogenic process can be modeled in the BBDR rat, which develops pancreatic insulitis and type 1A-like diabetes after infection with Kilham's rat virus (RV). The mechanism is unknown, but does not involve infection of the pancreatic islets. We first documented that RV infection of BBDR rats induces diabetes, whereas infection with its close homologue H-1 does not. Both viruses induced similar humoral and cellular immune responses in the host, but only RV also caused a decrease in splenic CD4(+)CD25(+) T cells in both BBDR rats and normal WF rats. Surprisingly, RV infection increased CD4(+)CD25(+) T cells in pancreatic lymph nodes of BBDR but not WF rats. This increase appeared to be due to the accumulation of nonproliferating CD4(+)CD25(+) T cells. The results imply that the reduction in splenic CD4(+)CD25(+) cells observed in RV-infected animals is virus specific, whereas the increase in pancreatic lymph node CD4(+)CD25(+) cells is both virus and rat strain specific. The data suggest that RV but not H-1 infection alters T cell regulation in BBDR rats and permits the expression of autoimmune diabetes. More generally, the results suggest a mechanism that could link an underlying genetic predisposition to environmental perturbation and transform a "regulated predisposition" into autoimmune diabetes, namely, failure to maintain regulatory CD4(+)CD25(+) T cell function.

Topics: Animals; Antibodies, Viral; Bromodeoxyuridine; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Coculture Techniques; Concanavalin A; Diabetes Mellitus, Type 1; Epitopes, T-Lymphocyte; Female; Genetic Predisposition to Disease; Immunity, Cellular; Interferon-gamma; Lymph Nodes; Lymphocyte Count; Lymphocytosis; Male; Pancreas; Parvoviridae Infections; Parvovirus; Poly I-C; Rats; Rats, Inbred BB; Rats, Inbred WF; Receptors, Interleukin-2; Spleen; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory

Bovine leukemia virus (BLV)-induced persistent lymphocytosis is characterized by a polyclonal expansion of CD5+ B lymphocytes. To examine the role of the cytokine microenvironment in this virus-induced B-lymphocyte expansion, the expression of interleukin-2 (IL-2), IL-4, IL-10, and gamma interferon (IFN-gamma) mRNA, was measured in stimulated peripheral blood mononuclear cells from persistently lymphocytotic BLV-infected cows, nonlymphocytotic BLV-infected cows, and uninfected cows. IL-2 and IL-10 mRNA expression and IL-2 functional activity were significantly increased when peripheral blood mononuclear cells from persistently lymphocytotic cows were stimulated with concanavalin A (ConA). Additionally, during persistent lymphocytosis, peak IL-2 and IL-10 mRNA expression was delayed, and elevated expression was prolonged. To determine the potential biologic importance of increased IL-2 and IL-10 expression, the response of isolated B lymphocytes from persistently lymphocytotic cows to human recombinant cytokines and to cytokine-containing supernatants from isolated T lymphocytes was examined. While recombinant human IL-10 (rhIL-10) did not consistently induce detectable changes, rhIL-2 increased viral protein (p24) and IL-2 receptor expression in isolated B lymphocytes from persistently lymphocytotic cows. Additionally, rhIL-2 and supernatant from ConA-stimulated T lymphocytes enhanced B-lymphocyte proliferation. The stimulatory activity of the T-lymphocyte supernatant could be completely inhibited with a polyclonal anti-rhIL-2 antibody. Finally, polyclonal anti-rhIL-2 antibody, as well as anti-BLV antibody, inhibited spontaneous proliferation of peripheral blood mononuclear cells from persistently lymphocytotic cows, demonstrating that the spontaneous lymphoproliferation characteristic of BLV-induced persistent lymphocytosis is IL-2 dependent and antigen dependent. Collectively, these findings strongly suggest that increased T-lymphocyte expression of IL-2 in BLV-infected cows contributes to development and/or maintenance of persistent B lymphocytosis.

Topics: Animals; Antigens, Viral; B-Lymphocytes; Cattle; Cell Division; Cells, Cultured; Concanavalin A; Culture Media, Conditioned; Gene Expression; Humans; Interleukin-10; Interleukin-2; Kinetics; Leukemia Virus, Bovine; Leukocytes, Mononuclear; Lymphocytosis; Mitogens; Receptors, Interleukin-2; Recombinant Proteins; RNA, Messenger; T-Lymphocytes; Viral Core Proteins

A single subcutaneous injection of 0.2 mg epinephrine into healthy human subjects caused a transient lymphocytosis in peripheral blood. Mononuclear cells (MNC), isolated at various times after epinephrine administration, were cultured in the presence of mitogens. The blastogenic responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were significantly reduced for up to 60 min post-epinephrine (p less than 0.05); the response to concanavalin A (Con A) was reduced in the 15-min samples only. All responses returned to pre-injection levels by 120 min post-injection. Removal of adherent monocytes from MNC isolates before culture did not restore normal mitogen responsiveness. When MNC were cultured in the absence of mitogens, there was no difference in survival between pre- and post-epinephrine samples. Incubation of untreated MNC for 2 hr or 18 hr in vitro with various concentrations of epinephrine (10(-5) to 10(-1) mg/ml) had no effect upon the subsequent blastogenic response to mitogens. Other workers have reported that epinephrine administration causes alterations in the composition of the circulating lymphocyte pool. Taken together, these data suggest that the reduction in mitogen responsiveness after epinephrine is the result of changes in the distribution of lymphocyte subclasses in peripheral blood.

Topics: Adult; Antibody-Producing Cells; Cell Survival; Concanavalin A; Cytoplasm; Epinephrine; Female; Humans; Immunoglobulins; Injections, Subcutaneous; Lymphocyte Activation; Lymphocytosis; Male; Mitogens; Monocytes; Phytohemagglutinins; Pokeweed Mitogens

Cytotoxic effector lymphocytes were induced in cultures of mouse spleen or lymph node cells by lymphocytosis promoting factor (LPF). The LPF-activated cytotoxic cells: (a) were not generated unless proliferation occurred; (b) sedimented in the lighter density fraction of a bovine serum albumin gradient; (c) were large, blast-like cells; and (d) were lysed by Thy-1.2 antiserum plus complement and, therefore, were T cells. Neither LPF alone nor supernates from stimulated cultures were cytotoxic. Unlike the situation with concanavalin A and phytohemagglutinin P, LPF-stimulated cytotoxic effector lymphocytes required no further addition of mitogen for maximal cytotoxicity. The effector cells displayed specificity, destroying only allogeneic but not syngeneic normal cells; in the case of tumor cells, both allogeneic and syngeneic cells werelysed in the absence of added mitogen. The reason for differentiated cytotoxicity toward syngeneic tumor and normal cells is not clear but may have some relevance to in vivo tumor rejection initiated by Bordetella pertussis.

Topics: Animals; Antilymphocyte Serum; Bordetella pertussis; Cell Division; Concanavalin A; Cytotoxicity, Immunologic; Female; Lymphocyte Activation; Lymphocytosis; Mice; Mice, Inbred Strains; Mitomycins; Neoplasms; Phytohemagglutinins; T-Lymphocytes

The lymphocytosis-promoting factor of Bordetella pertussis is a potent mitogen for murine lymphocytes in vitro. The stimulatory response was not the result of specific antigen stimulation. Spleen and lymph node cells were responsive, whereas normal thymocytes were unresponsive. However, DNA replication was induced in cortisone-resistant thymocytes by lymphocytosis-promoting factor (LPF). Bone marrow cells were not stimulated by LPF.

Topics: Animals; Antigen-Antibody Reactions; Bacterial Proteins; Bone Marrow; Bone Marrow Cells; Bordetella pertussis; Clone Cells; Concanavalin A; Cortisone; Female; Kinetics; Lectins; Lymph Nodes; Lymphocyte Activation; Lymphocytes; Lymphocytosis; Mice; Mice, Inbred CBA; Mice, Inbred Strains; Spleen; Thymus Gland

The mitogenic response of murine lymphocytes to the lymphocytosis-promoting factor of Bordetella pertussis has been shown to be due to activation of T cells. The selectivity of responsiveness to LPF with respect to the population of T cells which is stimllated, differs from that of PHA as well as Con A, and the surface receptors are different. A population of adherent cells, which does not appear to consist of macrophages or other phagocytic cells, is required for the T-cell response.

Topics: Animals; Antilymphocyte Serum; Bacterial Proteins; Bordetella pertussis; Cell Adhesion; Concanavalin A; Female; Isoantigens; Lectins; Lymphocyte Activation; Lymphocytosis; Macrophages; Mercaptoethanol; Mice; Mice, Inbred Strains; Mice, Nude; Microscopy, Electron; Spleen; T-Lymphocytes