Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons

Background. The human immunodeficiency virus type 1 ( HIV-1) epidemic is associated with a significant increase in the incidence of tuberculosis ( TB); however, little is known about the quality of Mycobacterium tuberculosis ( MTB)-specific cellular immune responses in coinfected individuals. Methods. A total of 137 HIV-1-positive individuals in Durban, South Africa, were screened with the use of overlapping peptides spanning Ag85A, culture filtrate protein 10 ( CFP-10), early secretory antigen target 6 ( ESAT-6), and TB10.4, in an interferon ( IFN)-gamma enzyme-linked immunospot ( ELISPOT) assay. Intracellular cytokine staining for MTB-specific production of IFN-gamma, tumor necrosis factor ( TNF)-alpha, and interleukin ( IL)-2 was performed, as was ex vivo phenotyping of memory markers on MTB-specific T cells. Results. A total of 41% of subjects responded to ESAT-6 and/or CFP-10, indicating the presence of latent MTB infection. The proportion of MTB-specific IFN-gamma(+)/TNF-alpha(+) CD4(+) cells was significantly higher than the proportion of IFN-gamma(+)/IL-2(+) CD4(+) cells ( P = .0220), and the proportion of MTB- specific IL-2-secreting CD4 cells was inversely correlated with the HIV-1 load ( P = .0098). MTB- specific CD8 T cells were predominately IFN-gamma(+)/TNF-alpha(+)/IL-2(-). Ex vivo memory phenotyping of MTB- specific CD4 and CD8 T cells indicated an early to intermediate differentiated phenotype for the population of effector memory cells. Conclusions. Polyfunctional MTB- specific CD4 and CD8 T cell responses are maintained in the peripheral blood of HIV-1-positive individuals, in the absence of active disease, and the functional capacity of these responses is affected by HIV-1 disease status.