Pathogen prevalence may determine maintenance of antigen-specific T-cell responses in HIV-infected individuals

OBJECTIVE To assess the effect of antigen-exposure on the T-cell repertoire in the chronic phase of HIV-infection. DESIGN This is a prospective cross-sectional study. METHODS HIV-seropositive patients and immunocompetent controls from tuberculosis low and high-endemic countries were recruited. Mycobacterium tuberculosis (purified protein derivative; PPD)-specific CD4 T-cell responses were quantified directly from whole blood using flow-cytometric analysis of intracellular cytokines after specific stimulation. T-cell reactivity toward cytomegalovirus (CMV) or Staphylococcus aureus Enterotoxin B (SEB) served as control. RESULTS In a low-endemic region, HIV-seropositive patients showed lower frequencies of PPD-specific T cells compared to immunocompetent individuals. This was not due to a general loss of immunity toward recall antigens, as T-cell immunity toward CMV or SEB was preserved. In line with continuous antigen exposure, HIV-seropositive patients from a high-endemic region showed preserved PPD-specific T-cell frequencies that were not different from those found in HIV-seronegative controls. Likewise, both groups did not differ in recall T-cell responses toward CMV or SEB. CONCLUSION A lower prevalence and frequency of PPD-specific immunity is a typical feature of HIV-related immunosuppression in low-endemic regions. In contrast, PPD-specific responses are maintained in HIV-seropositive individuals in regions with high tuberculosis prevalence. This suggests constant skewing and restriction of specific T-cell immunity toward environmental antigens in HIV-seropositive individuals.