Immunopathogenesis of the acquired immunodeficiency syndrome.

Many abnormalities of humoral and cellular immunity associated with the acquired immunodeficiency syndrome (AIDS) can be explained by the preferential infection of the T4 lymphocyte subset with the etiologic retrovirus. Qualitative T-cell defects noted in AIDS patients include decreased blast transformation to mitogens and antigens, decreased lymphokine production, decreased alloreactivity, diminished cytotoxic cell response, and depressed helper function for B-cell immunoglobulin production. B lymphocytes are polyclonally activated in these patients. Theoretically, human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) infection may infect some subsets of immune cells, leading to a predominant cytopathic effect. In this situation, suppressed immune function may be due to a quantitative deficiency of the cell responsible for the function in question. Other cells may be infected by the virus in the absence of a resultant cytopathic effect, in which case suppressed immune function may be due to a quantitative effect in cells related directly or indirectly to genomic alterations. Recent data suggest that the T4 receptor may partially represent the membrane acceptor for infection by the etiologic virus. Further studies showed that preincubation of lymphocytes with monoclonal antibodies to distinct epitopes of the T4 glycoprotein blocked susceptible cell infection by LAV. The entire array of immunologic abnormalities may be explained by altered functions of the T4 inducer/helper lymphocyte subset. Such data lead to a hypothetic scheme for selective HTLV-III/LAV infection of the T4 helper/inducer lymphocyte and the resultant devastating effect this has on immune function in AIDS. Because of its central role in the induction and evolution of normal immune function by other effector cells, it is easy to see how a selective depletion or disruption of function of the T4 lymphocyte by HTLV-III results in severely altered, life-threatening immunity.