Acquired immunodeficiency syndrome (AIDS) is associated with a viral (HTLV-III) mediated progressive depletion of the helper/inducer T4+ T cell subset, whereas acute T cell leukemia is associated with viral (HTLV-I) mediated growth of the same T cell subset. We have recently demonstrated that large granular lymphocytes (LGL) with natural killer activity have been able to spontaneously lyse several types of virus infected target cells. The ability of IL 2 to greatly augment NK lysis of both HTLV-I and HTLV-III infected lymphoid cells and fresh lymphocytes in vitro was also shown. IL 2 activated T cells and NK cells were cytolytic for HTLV-I infected target cells. However, only large granular lymphocytes demonstrate significant spontaneous activity against HTLV-I and HTLV-III targets. In addition, the differentiation antigen T4 is present on the helper/inducer T cell subset, which is responsible for the humoral regulation of immune reactivity and hematopoietic development. In AIDS, this lymphocyte subset is selectively depleted by infection with HTLV-III virus which apparently uses the T4 antigen complex on the T-cell surface as a viral receptor. Since patients with AIDS frequently develop CNS symptoms, we investigated sites of entry of HTLV-III in monkey brains. Autoradiographic visualization revealed T4 antigen on thin coronal sections of squirrel monkey brain in a strikingly heterogeneous pattern with clustering in the same emotionmediating nodal points of the brain that are usually enriched with neuropeptide receptors Immunoprecipitates of radiiodinated cell membranes prepared from primate brain indicate that an antigen very similar to T4 antigen is present on brain as well as on T4+ T-lymphocytes. Other T lymphocyte associated antigens such as T8 were not found in the brain. Since patients with AIDS frequently develop symptoms involving the central nervous system and HTLV-III sequences have been found in the brain, these data suggest that direct infection of some brain cells with HTLV-III occurs via a mechanism involving the T4 antigen similar to that in lymphocytes. Finally, based on our findings of the presence of receptors for cytokines, and pathogenic viruses in the immune and central nervous systems, we have studied the ability of neuronal peptides to inhibit HTLV-III infection. Several synthetic peptides based on known sequences of neuronal peptides were designed as possible competitive analogues against HTLV-III infectivity.
