Candida albicans Protective Immune Responses in HIV Patients and Controls

Objectives: This study aimed to investigate the role of protective interferon-µ responses to candidiasis and the function of gamma delta T-cells in this process. As HIV disease progresses towards AIDS, susceptibility to oropharyngeal candidiasis (OPC) increases. Highly active antiretroviral therapy (HAART) promotes immune reconstitution. However some HIV-positive patients responding to HAART present with OPC. Methods: Interferon-γ ELISpot assays were used to examine responses to Candida antigens in peripheral blood mononuclear cells from HIV-positive patients who had been on HAART for 0-9 years and HIV-negative patients with and without OPC. Cultures were stimulated with a crude lysate (Candia5) or an enolase protein antigen. The percentage of γδ T-cells, senescent T-cells (marked by CD57)and regulatory T-cells (marked by CD25) were also assessed by flow cytometry, to discern their role in systemic immunity to Candida spp. Results: Interferon-γ ELISpot responses were higher in of HIV-negative donors without symptomatic OPC (n=15) than HIV patients (56 samples from 18 patients) whilst HIV-negative patients with OPC (n=3) responded poorly. HIV patient responses increased when CD4 T-cell counts rose and viral load was controlled for the first 5 years on HAART. However after 5 years of HAART, a decreased response was detected despite maintained control of viral load and reconstituted levels of CD4 T-cells. Significantly higher responses were found in HIV patients with undetectable viral load and CD4 T-cell counts greater than 200 cells/mm3. γδ T-cells in the periphery increased with time on HAART. They were more highly activated (marked by CD38) in HIV patients compared to controls. HAART patients had higher levels of T-cell senescence and this correlated with low ELISpot responses. Conclusions: The study validates interferon-γ as a method of assessment of protective immunity to Candida spp. It suggests a role of T-cell senescence in limiting the responses of HIV patients to Candida antigens.