Infection with the human immunodeficiency virus (HIV- 1) leads to a breakdown of the immune system with the development of both opportunistic infections and malignancies including lymphomas and Kaposi's sarcoma. Although direct destruction of CD4+ T cells is a cause of the developing immunodeficiency in clinical AIDS, immunologic abnormalities can be documented in early HIV infection before a significant drop in CD4+ T cells occurs. While several investigators have demonstrated that there is a selective loss of memory T cell helper cells in early clinical HIV infection, no consistent changes have been seen in asymptomatic patients, and no hypothesis has been forthcoming which can explain all of the immunologic alterations. We have developed a monoclonal antibody, B721, which recognizes a T cell activation antigen, and defines subset of activated cells derived from the CD45RA+ precursor population of CD4 cells. We have also shown that this subset of activated cells responds to TGFBeta1, and appears to be phenotypically and functionally distinct from IL-4 responsive precursor cells. We have generated evidence that this subset of cells is abnormally activated in early HIV infection, and given that it has recently been shown that TGFBeta1 is elevated in HIV infection, we propose that the activation of these cells is not coincidental, and this subset may play a role in the early immunologic abnormalities seen in HIV infection. We have designed a series of experiments to examine the possible functions of the B721+ CD4 T cell subset, and present preliminary evidence that it may be similar to a subset of CD4 precursor cells known to have suppressor/inducer function. We believe that these data are important because B721 is the first marker which appears to subdivide the cells arising from the precursor CD4 T cell population in humans, and our evidence is the first indication that a specific T cell subset is abnormally activated in HIV infection. We believe that these observations and studies are important in contributing to our understanding of the pathogenesis of AIDS.
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