The cytotoxic T cell response to HIV

Abstract

The normal immune response to an infectious organism involves both non-specific and antigen-specific immunity. Virus infections stimulate specific antibodies, T-helper cells and cytotoxic T cells (CTL). The importance of virus-specific CTL in the clearance of viral infections has been increasingly recognized over the past decade, and it is likely that CTL form the major specific defence against primary virus infections. Evidence for the in vivo role of virus-specific CTL comes from experimental animal models and, in addition, a few studies in humans. Following influenza A virus infection, CTL specific for influenza are generated, detectable before the primary IgM response1, and help in the clearance of the infection. In experimental mouse models of influenza infection, cloned influenza-specific CTL have been adoptively transferred to infected mice with resulting clearance of the virus from the lungs2, and in a comparison of humoral and cell-mediated immunity, antibody failed to clear the virus infection whereas CTL cultures eliminated the virus3. CD4+ T cell-depleted mice generate viral-specific CTL which clear influenza virus from the lungs4 and assist in recovery from ectromelia virus infection5. CD8+ T cells have also been shown to be actively involved in the elimination of retrovirus-induced tumours6. In humans the rapid clearance of nasal virus after deliberate infection with influenza A virus has been correlated with specific CTL activity7, and control of primary and latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections has also been associated with circulating CTL activity8, 9, 10. This accumulating evidence points to a major role of CTL in the elimination of virally infected cells. As retrovirus-specific CTL have been shown to be of great importance in the immune attack against retrovirus-induced mouse tumours6, 11, and human HTLV-I-specific CTL have been detected from HTVL-I-infected patients12, 13, 14, several groups of scientific investigators looked for HIV-specific CTL in HIV-infected individuals.