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N Chirmule

Publications and source records attributed to N Chirmule.

60 records · Page 4Linked to original sources

Requirement of the T cell receptor for antigen presentation by T lymphocytes. Effect of envelope glycoproteins of HIV-1 on antigen presentation by T cells.

We have developed CD4+, tetanus antigen-specific T cell clones that proliferate in the presence of tetanus antigen and autologous irradiated peripheral blood leucocytes (PBL) as antigen-presenting cells (APC). There have been several reports that T cells can present antigen themselves. We have used tetanus antigen-specific T cell clones to examine the effects of envelope glycoproteins of HIV-1 on processing and presentation of antigen to T cells. Cloned T cells were pre-incubated with soluble crude preparation of tetanus antigen for 4 h at 37 degrees C, irradiated, and used as APC (T-APC). These cells could present antigen, as assessed by the ability of the autologous cloned T cells to proliferate. Resting T cells and phytohaemagglutinin-activated T cell blasts from autologous PBL could not present tetanus antigen to the responder cloned T cells. Antigen presentation by T-APC was abrogated by treating cells with anti-HLA-DR but not by anti-HLA-DQ monoclonal antibodies; treatment of tetanus antigen-pulsed T-APC with anti-tetanus antibody also blocked the ability of these cells to induce proliferation in responder T cells. Antigen presentation by cloned T cells was by a chloroquine-resistant pathway. Pretreatment of T-APC with envelope glycoprotein of HIV-1, gp120, did not affect the proliferative responses of the responder T cells. These data suggest that gp120 does not inhibit the antigen-presenting function while suppressing antigen-specific responses.

Antibodies, Monoclonal↗

In vitro synthesis of human immunodeficiency virus-specific antibodies in peripheral blood lymphocytes of infants.

An assay system was developed for the analysis of antibodies secreted in vitro against human immunodeficiency virus (HIV) by cultured peripheral blood lymphocytes of HIV-infected individuals. Cultures of peripheral blood lymphocytes were established with medium alone or with medium containing Epstein-Barr virus (EBV) or pokeweed mitogen. HIV antibodies were determined by an ELISA performed with commercial kits in which a whole virus extract served as antigen. Optimal antibody secretion was detected in 7-day peripheral blood lymphocyte cultures to which EBV had been added to provide polyclonal B-cell activation. Pokeweed mitogen-induced antibody secretion and spontaneous antibody secretion were less consistent. With EBV as a stimulus, the sensitivity and specificity of this assay for determining HIV infection status were each 100% in adults. When the assay was applied to infants and children, 23 of 24 symptomatic HIV-seropositive children (class P-2) and 11 of 33 asymptomatic seropositive infants aged less than or equal to 15 months (class P-0) tested positive for EBV-induced antibody secretion. Six of the 11 P-0 patients who tested positive have progressed to develop symptomatic disease, while the remainder are still seropositive at ages 2-15 months. Of the infants who were negative in this assay, all have remained asymptomatic. Treatment with 3'-azido-3'-deoxythymidine in infected adults and children has resulted in transient suppression of the in vitro antibody response in some instances. Thus EBV-induced synthesis of HIV-specific antibodies in vitro is a sensitive and specific indicator of HIV infection and is of help in determining infection status of asymptomatic seropositive infants who are classified as having "indeterminate" infection.

Acquired Immunodeficiency Syndrome↗

Influences of related retroviruses on lymphocyte functions.

The human immunodeficiency virus (HIV-1) is known to be profoundly immunosuppressive [Spickett and Dalgleish (1988) Clin. Exp. Immunol. 71, 1]. In this communication, we have studied the influences of HIV-1 (BH10), HIV-2 (LAV-2) and STLV-3 on B and T cells from healthy volunteers. B lymphocytes were found to differentiate into immunoglobulin secreting cells in response to stimulation by proteins of HIV-1 and LAV-2, but not by STLV-3. This response was obtained at protein concentrations of 0.05-0.005 micrograms/ml and was T cell dependent. IgM secretion was induced only by HIV-1 in the EBV-transformed B cell line SKW 6.4. At higher concentrations all three retroviral preparations had inhibitory influences on functions of B as well as T lymphocytes. B cell differentiation was maximally inhibited by HIV-1 and LAV-2 when these proteins were added concurrently to cultures with the polyclonal B cell activators pokeweed mitogen or Epstein-Barr virus. Tetanus antigen-specific T cell lymphoproliferation was inhibited by all retroviral proteins. These findings suggest that related retroviruses differ in their capacity to influence normal immune responses.

Cell Differentiation↗

Inhibitory influences of envelope glycoproteins of HIV-1 on normal immune responses.

Infection with the human immunodeficiency virus (HIV-1) leads to a wide range of immunological abnormalities. We have shown that native envelope glycoproteins (gp120) of HIV-1 inhibit antigen-specific and anti-CD3 induced lymphoproliferation of normal lymphocytes. We have demonstrated that gp120 binds to CD4 positive T lymphocytes and is internalized. These studies suggest that interaction of gp120 with the CD4 receptor may be sufficient to inhibit antigen-specific T cell responses that are mediated via the CD3-Ti receptor complex. Such an event could represent another mechanism by which the overall immune function of the CD4 positive T lymphocyte is depressed and may be relevant in planning investigations on the ongoing vaccine trial involving envelope glycoproteins.

Antigens, Differentiation, T-Lymphocyte↗

AIDS.

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Acquired Immunodeficiency Syndrome↗