Concanavalin A triggers T lymphocytes by directly interacting with their receptors for activation.

Anti-HLA-DR antibodies did not inhibit concanavalin A-(Con A) induced T cell proliferation or the generation of suppressor cells capable of inhibiting immunoglobulin synthesis in autologous mononuclear cells after pokeweed mitogen stimulation. Nylon-wool purified T cells (pretreated with anti-HLA-DR antibody and C) exposed to Con A acquired responsiveness to interleukin 2 (IL 2) and were able to absorb this growth factor, whereas nonlectin-treated cells did not respond to IL 2 and could not absorb it. In the presence of interleukin 1 (IL 1), Con A stimulated the synthesis of IL 2 in purified OKT4+ lymphocytes but not OKT8+ cells.

Epstein-Barr virus increases the proliferative response and the generation of suppressor and cytotoxic T-cell functions in autologous mixed lymphocyte reaction.

Epstein-Barr virus (EBV) infection of stimulator cells significantly increased the proliferative response of T cells in the autologous mixed lymphocyte reaction (AMLR). The addition of a monoclonal anti-HLA-DR antibody to AMLR cultures in which either EBV-infected or non-infected non-T cells were used as stimulator cells strongly inhibited the proliferative response irrespective of the presence of EBV. It is concluded that EBV does not by itself activate the responding cells and that HLA-DR antigens are necessary to trigger T cells.

Human postthymic precursor cells in health and disease. IV. Abnormalities in immunoregulatory T cell circuits in mixed connective tissue disease.

Human T cells are capable of forming rosettes with autologous erythrocytes (Tar cells) and behave as postthymic precursors. Thus, they generate Tgamma and Tmu cells as well as suppression and spontaneous cytotoxicity and participate in a pokeweed mitogen-driven system akin to that of feedback inhibition in which murine postthymic precursors participate. Tar cells were increased in 7 patients with mixed connective tissue disease (MCTD) compared to normal age/sex-matched controls.

HLA-DR antigens render interleukin-2-producer T lymphocytes sensitive to interleukin-1.

Monoclonal anti-HLA-DR antibodies inhibited the production of interleukin-2 (IL-2) when added from the initiation of autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reactions, but not 60 h later. The inhibitory activity of the anti-DR sera became apparent 8 h after initiation of the cultures and was maintained throughout the culture period. Interleukin-1 (IL-1) added to cultures carried out in the absence of the anti-DR antibodies significantly enhanced the production of IL-2, whereas addition of IL-1 to anti-DR-treated AMLR and MLR cultures did not restore or increase the synthesis of IL-2.

Differences in immunoregulatory T cell circuits between diphenylhydantoin-related and spontaneously occurring systemic lupus erythematosus.

We studied T cell surface markers, concanavalin A-induced, and spontaneously expanded suppressor cell function and the functions of postthymic precursor (Tar) cells in 3 patients with diphenylhydantoin (DPH)-related systemic lupus erythematosus (SLE). The findings were compared with those in 6 patients with spontaneously occurring SLE, 3 with active and 3 with inactive disease as well as with those in 3 normal volunteers. All 4 groups were age and sex matched.

T cell growth factor abrogates concanavalin A-induced suppressor cell function.

Concanavalin A (Con-A)-induced suppressor T cells were found to respond to T cell growth factor (TCGF) by proliferation. TCGF abrogated the suppressor activity exerted by these cells on phytohemagglutinin (PHA)- and alloantigen- induced lymphocyte proliferation and on pokeweed mitogen (PWM)-driven immunoglobulin secretion. The Con-A-activated suppressor T cells absorbed the TCGF activity, preincubation of these active suppressor cells with TCGF abolished their suppressor activity and addition of increasing numbers of Con-A-activated T cells reverted the abrogator,/ effect of TCGF.

Human postthymic precursor cells in health and disease. VII. Immunoregulatory circuits of the peripheral blood mononuclear cells from patients with progressive systemic sclerosis.

The study of T cell subpopulations and their immunoregulatory circuits in 9 patients with progressive systemic sclerosis (PSS) and 9 age/sex matched controls showed: 1. Normal postthymic precursor autologous rosette-forming T cells (Tar cells). 2.

Cimetidine abrogates suppressor T cell function in vitro.

Cimetidine increased the [3H] thymidine incorporation of normal human mononuclear cells in culture both when unstimulated or when under the stimulus of phytohemagglutinin or pokeweed mitogen (PWM). It also increased their supernatant immunoglobulin production under PWM stimulus. These effects were higher when the cells were preincubated with cimetidine than when it was added simultaneously.

Human post-thymic precursor cells in health and disease. IX. Immunoregulatory T cell circuits in peripheral blood of patients with rheumatoid arthritis.

We studied T cell subpopulations and their immunoregulatory circuits in the peripheral blood of 16 patients with rheumatoid arthritis (RA) who were receiving no medications that might interfere with the results. We found normal T cells with receptors for the Fc portion of IgG or IgM as well as autologous rosette-forming T cells (Tar cells), a subpopulation of T cells we have found to have the properties of human post-thymic precursors. We also found that peripheral blood cells of RA patients have normal concanavalin A-induced or spontaneously-expanded suppressor cell functions.

Human postthymic precursor cells in health and disease. II. Their loss and dysfunction in systemic lupus erythematosus and their partial correction with serum thymic factor.

We have recently described that human autologous rosette-forming (Tar) cells have the characteristics of postthymic precursor cells. Herein we report that we found circulating Tar cells significantly diminished in 32 patients with untreated systemic lupus erythematosus (SLE) as compared to 32 age/sex matched controls. Pretreatment of peripheral blood mononuclear cells (MNC) from SLE patients with serum from young normal adults or wtih serum thymic factors (FTS) increased their percentages of Tar cells significantly but reached near normal values in only 3 patients with inactive disease.

HLA-DR antigens induce proliferation and cytotoxicity of T cells against haptenated (TNP and FITC) self structures.

Antisera directed against the heavy, the light, or reactive against the complex of both chains of HLA-DR antigens strongly inhibited proliferation of T cells induced by TNP- or FITC-labeled autologous cells when added at initiation of the cultures, but not 72 h later. T cells from cultures treated with the anti-DR sera were unresponsive to interleukin-2 (IL-2). Nonetheless, the anti-DR sera did not inhibit proliferation of T cells that had already acquired sensitivity to IL-2.

Human post-thymic precursor cells in health and disease. I. Characterization of the autologous rosette-forming T cells as post-thymic precursors.

Human autologous-rosette-forming T cells (Tar cells) have many of the characteristics of post-thymic precursor cells. Thus, they bind to sheep erythrocytes but have neither receptors for the Fc portion of IgG nor for that of IgM. They include a subpopulation that binds peanut agglutinin which suggests that they are immature and, as opposed to T cells with either receptors for the FC portion of IgM (T mu) or of IgG (T gamma), Tar cells adhere to nylon wool, another possible indicator of immaturity, as is their extreme sensitivity to hydrocortisone both in vitro and in vivo.

Role of individual chains of HLA-DR antigens in activation of T cells induced by alloantigens.

The role of HLA-DR antigens in the activation of T cells in the allogeneic mixed lymphocyte reaction (MLR) was studied by using antibodies raised against the alpha, beta or the complex of both chains of the HLA-DR antigens. Antisera directed against the alpha or the beta chain strongly inhibited the T-cell proliferative response when added at the beginning of MLR cultures but not 72 h later. T cells from MLR cultures treated with either alpha-chain- or beta-chain-specific antibodies did not respond to interleukin-2 (IL-2) by proliferating, whereas T cells from non-anti-DR-treated cultures showed a proliferative response to IL-2-stimulation.

Human post-thymic precursor cells in health and disease. III. Role of the autologous rosette-forming T cells in the generation of spontaneous killer cells in the autologous mixed lymphocyte reaction.

Adult peripheral blood T lymphocytes activated in autologous mixed lymphocyte reactions (AMLR) exerted cytotoxicity on both phytohaemagglutinin-stimulated cells and Epstein-Barr virus-transformed cells. When autologous rosette-forming T cells were removed from total T lymphocytes, there was no generation of cytotoxicity. Re-addition of autologous rosette-forming T cells (Tar cells) to a population of T cells depleted of Tar cells restored the cytotoxic activity.

Cyclosporin A abrogates proliferation of T cells and generation of suppressor and cytotoxic T-cell function induced by Epstein-Barr virus.

Cyclosporin A (CYA) promotes the outgrowth in vitro of Epstein-Barr-virus(EBV)-infected cells of immune donors. In the present study, the effects of CYA on the T-cell responses developed to an in-vitro EBV infection were studied. Cyclosporin A, by acting on the responder cells and not on stimulator cells, strongly inhibited the proliferation of T cells normally induced by EBV-infected autologous cells.