Lack of infection in HIV-exposed individuals is associated with a strong CD8⁺cell noncytotoxic anti-HIV response

Abstract

Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8؉ -cell noncytotoxic inhibition of HIV replication in acutely infected CD4 ؉ cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8 ؉ -cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 ⌬32 mutation in this population, nor did CD4؉ cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8 ؉ -cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.

Parenteral exposure to high HIV viremia leads to virus‐specific T cell priming without evidence of infection

“…Their immune system is likely able to keep the virus under control and the analysis of their immune response may provide important information about the immunological correlates of protection [12]. Further information in this respect can derive from the study of HIV-exposed individuals [13,14] who show resistance to infection. Host genetic factors, including genetic variation of chemokine receptors and immunological factors, such as overproduction of b-chemokines and type of HIV-specific CTL responses, have been proposed to explain the lack of infection [15].…”

IL-22 Participates in an Innate Anti-HIV-1 Host-Resistance Network through Acute-Phase Protein Induction

“…Additional resistance to HIV-1 infection is reportedly associated with the activity of HIV-1-specific helper and CTL (2,6,7) and with enhanced local mucosal IgA responses (8). Moreover, an association between resistance to HIV-1 infection and enhanced NK activity (9), as well as increased production of IFN-␥ produced by CD4 T cells (10), CD8 antiviral factors (11), and defensins (12) has been described. More recently, the frequencies of CD4 ϩ and CD8 ϩ CD45RA Ϫ CCR7 ϩ central memory cells, as well as terminally differentiated CD8 ϩ CD45RA ϩ CCR7 Ϫ and CD27 Ϫ CD28 Ϫ T lymphocytes, were reported to be increased in EU, compared with HIV-1-infected patients (13), suggesting a role for the latter cells in preventing actual infection.…”

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

“…In tissue culture, CTL recognizing early proteins killed HIV-infected cells before they produced more virus virions, 22,23 and produced chemokines that inhibit HIV replication. [24][25][26][27] In vivo, vaccineinduced CTL against early proteins provided a degree of protection against pathogenic virus challenges. [28][29][30] However, the protective role of Tat alone has been controversial.…”