Possible protective and pathogenic roles of gamma delta T lymphocytes in HIV-infections (Review).

alpha beta and gamma delta T lymphocytes are largely responsible for the specificity of coordinated immune responses that are of crucial importance for protection from exogenous invaders and elimination of endogenous aberrations. One of the prominent distinguishing characteristics of primate gamma delta T lymphocytes is that most of their T cell receptors for antigen (gamma delta TCRs) are, unlike alpha beta TCRs, capable of recognizing nonpeptidic antigens in an MHC-unrestricted manner. Another interesting feature is that the gamma delta T cell subpopulation displays profound qualitative and quantitative changes in individuals with various infectious diseases. For example, the most frequent human peripheral blood gamma delta T cell subset expressing Vgamma9Vdelta2 TCRs is functionally disabled and numerically decreased in some HIV-infected persons. The nonresponsiveness of Vgamma9Vdelta2 T cells is accompanied by their decreased IFNç and TNFá production. The overall level of gamma T cell activation at different stages of HIV-infection may be clinically relevant. At an initial stage of HIV-infection, the extremely potent antiviral cytotoxic activities of Vgamma9Vdelta2 T cells may limit the viral spread. At later stages of disease, Vgamma9Vdelta2 T cell dysfunction may contribute to the loss of resistance to opportunistic pathogens (such as atypical mycobacteria) and neoplasms (e.g., lymphomas) frequently associated with HIV-infections. Also, it is possible that chronic stimulation of gamma delta T cells may result in immunopathology. In particular, the massive immunologic activation that appears to be the major contributing element of AIDS immunopathogenesis could be, at least in part, driven by gamma delta T cells overstimulated by repetitive exposures to HIV.