Background:  Among the HIV-infected population exists a unique group of individuals who achieve control over HIV replication in the absence of ART. The study of such individuals is crucial to understanding how the immune system may effectively control viral replication and limit progression to AIDS.  

Methods:  In this study we examined cell-mediated immune responses in 26 HIV controllers (viral load <2000 copies/mL), 14 non-controllers (viral load >10,000 copies/mL), and 10 HAART-suppressed individuals (viral load <50 copies/mL) in peripheral blood mononuclear cells (PBMC) and rectal mucosa. Of the controllers, 14 were classified as elite controllers, individuals who maintain plasma viral load <75 copies/mL in the absence of ART. This group is believed to encompass <1% of all HIV-infected individuals. In intracellular cytokine assays, we measured the production of 3 cytokines (interferon-γ, interleukin-2, tumor necrosis factor-α), 1 chemokine (MIP-1β), and the cytolytic granule marker CD107 in response to stimulation by HIV-1 Gag peptides. We hypothesized that “polyfunctional” T cells, capable of producing multiple antiviral factors, are critical in limiting viral replication and disease progression.

Results:  Mucosal CD8 T cell responses in controllers were significantly stronger and more complex than those in HAART-suppressed individuals (p = 0.0006). Differences between controllers and non-controllers were more subtle, but included a higher frequency of 4-function HIV-specific CD8 T cells in rectal mucosa of controllers than in non-controllers (p = 0.002). CD4 T cell responses were less complex and of lower magnitude than CD8 responses, but several controllers had unusually strong, polyfunctional mucosal CD4 responses.

Conclusions:  These findings demonstrate that many controllers mount strong and complex HIV-specific T cell responses in mucosal tissues. These polyfunctional cells may play an important role in immune surveillance of gut mucosa, as suggested by their relative enrichment among individuals who appear to be controlling HIV replication in absence of therapy.