Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

Loss of immune control over opportunistic infections can occur at different stages of hiv-1 (hiv) disease,among which mucosal candidiasis caused by the fungal pathogen candida albicans (c. albicans) is one of the early and common manifestations in hiv-infected human subjects. the underlying immunological basis is not well defined. we have previously shown that compared to cytomegalovirus (cmv)-specific cd4 cells,c. albicans-specific cd4 t cells are highly permissive to hiv in vitro. here,based on an antiretroviral treatment (art) naïve hiv infection cohort (rv21),we investigated longitudinally the impact of hiv on c. albicans- and cmv-specific cd4 t-cell immunity in vivo. we found a sequential dysfunction and preferential depletion for c. albicans-specific cd4 t cell response during progressive hiv infection. compared to th1 (ifn-γ,mip-1β) functional subsets,the th17 functional subsets (il-17,il-22) of c. albicans-specific cd4 t cells were more permissive to hiv in vitro and impaired earlier in hiv-infected subjects. infection history analysis showed that c. albicans-specific cd4 t cells were more susceptible to hiv in vivo,harboring modestly but significantly higher levels of hiv dna,than cmv-specific cd4 t cells. longitudinal analysis of hiv-infected individuals with ongoing cd4 depletion demonstrated that c. albicans-specific cd4 t-cell response was preferentially and progressively depleted. taken together,these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in hiv-infected patients and provide new insights into pathogen-specific immune failure in aids pathogenesis. © 2016 this is an open access article,free of all copyright,and may be freely reproduced,distributed,transmitted,modified,built upon,or otherwise used by anyone for any lawful purpose.