POSSIBLE PROTECTIVE AND PATHOGENIC ROLES OF GAMMA-DELTA T-LYMPHOCYTESIN HIV-INFECTIONS (REVIEW)

alpha beta and gamma delta T lymphocytes are largely responsible for t he specificity of coordinated immune responses that are of crucial imp ortance for protection from exogenous invaders and elimination of endo genous aberrations. One of the prominent distinguishing characteristic s of primate gamma delta T lymphocytes is that most of their T cell re ceptors for antigen (gamma delta TCRs) are, unlike alpha beta TCRs, ca pable of recognizing nonpeptidic antigens in an MHC-unrestricted manne r. Another interesting feature is that the gamma delta T cell subpopul ation displays profound qualitative and quantitative changes in indivi duals with various infectious diseases. For example, the most frequent human peripheral blood gamma delta T cell subset expressing V gamma 9 V delta 2 TCRs is functionally disabled and numerically decreased in s ome HIV-infected persons. The nonresponsiveness of V gamma 9V delta 2 T cells is accompanied by their decreased IFN gamma and TNF alpha prod uction. The overall level of gamma delta T cell activation at differen t stages of HIV-infection may be clinically relevant. At an initial st age of HIV-infection, the extremely potent antiviral cytotoxic activit ies of V gamma 9V delta 2 T cells may limit the viral spread. At later stages of disease, V gamma 9V delta 2 T cell dysfunction may contribu te to the loss of resistance to opportunistic pathogens (such as atypi cal mycobacteria) and neoplasms (e.g., lymphomas) frequently associate d with HIV-infections. Also, it is possible that chronic stimulation o f gamma delta T cells may result in immunopathology. In particular, th e massive immunologic activation that appears to be the major contribu ting element of AIDS immunopathogenesis could be, at least in part, dr iven by gamma delta T cells overstimulated by repetitive exposures to HIV.