There is abundant evidence that some individuals can repel HIV infection despite extensive exposure to the virus. The evidence comes from multiple sources, such as the well-publicized cohort of women sex workers in Nairobi, studies of couples discordant for HIV infection and babies exposed to high levels of HIV both in utero and via breastfeeding. The mechanisms of protection, however, remain elusive and controversial.
A new study in Clinical & Vaccine Immunology now adds to the literature on this subject. Thirty couples discordant for HIV infection with a history of unprotected sex were involved in the study. Uninfected partners were studied for evidence of T cell immunity against HIV, and results were compared to those obtained from individuals infected with HIV and an uninfected control group. The researchers found that peripheral blood mononuclear cells (PBMC) from the exposed uninfected (EU) individuals released high levels of IL-2 after stimulation with the HIV p24 Gag antigen. These levels of IL-2 production were significantly higher than those seen in both infected individuals and uninfected controls. Furthermore, there was a strong inverse correlation between the levels of IL-2 production in the EU individuals and the time since their last unprotected exposure to HIV, suggesting that exposure was boosting HIV-specific immunity rather than leading to infection. The researchers note that, while the PBMC-based IL-2 release assay is not optimal, it likely provides a reasonable surrogate for the presence of HIV-specific CD4 T cells capable of making IL-2. The researchers also looked at HIV-specific CD8 T cell responses by assessing expression of the cell-killing substances perforin and granzyme B after stimulation of CD8 T cells with HIV Gag p24. In this case, infected individuals displayed the highest response but responses in EUs were also significantly higher than in the controls. Again, there was an inverse correlation between the magnitude of the HIV-specific CD8 T cell response and time since the last unprotected exposure to HIV. There was also a positive correlation between the magnitude of HIV-specific IL-2 production and the magnitude of the HIV-specific CD8 T cell response.
The critically important question, of course, is whether the presence of HIV-specific immune responses in these individuals is just a marker of exposure to HIV or an indication that these immune responses are protecting against the acquisition of HIV infection. Ongoing efficacy trials of vaccines that induce HIV-specific CD4 and CD8 T cell responses should be able to answer this question within the next few years.
Clin Vaccine Immunol. 2007 Sep;14(9):1196-202.
Pallikkuth S, Wanchu A, Bhatnagar A, Sachdeva RK, Sharma M.
Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Repeated exposure to human immunodeficiency virus (HIV) does not always result in HIV infection, and several cohorts of HIV-exposed but uninfected (EU) individuals have been described. We studied T-helper and granule-dependent cytotoxic T-lymphocyte (CTL) activities in a group of 30 EU partners of HIV type 1 (HIV-1)-infected individuals. HIV-1-specific helper-T-cell activity was studied by measuring the levels of interleukin 2 (IL-2) produced by peripheral blood mononuclear cells (PBMCs) and the granule-dependent CTL activity by measuring the intracellular levels of perforin and granzyme B expression in CD8(+) T cells after stimulation with gag p24 antigen. Elevated IL-2 production by PBMCs after p24 stimulation occurred in EU individuals. The levels of perforin and granzyme B expression in CD8(+) T cells were also higher among EU individuals than among healthy controls. HIV-specific helper-T-cell and granule-dependent CTL activities inversely correlated with the time since the last unprotected sexual exposure in these individuals. In our cohort, activation of T-helper and granule-dependent CTL activities against HIV might be due to unprotected sexual contact. These results indicate that HIV-1-specific T-cell responses could play a role in protection against acquiring infection in this cohort of EU individuals.
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