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.
Day
Cheryl L
CL
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa. cheryl.day@uct.ac.za
Mkhwanazi
Nompumelelo
N
Reddy
Sharon
S
Mncube
Zenele
Z
van der Stok
Mary
M
Klenerman
Paul
P
Walker
Bruce D
BD
D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013019:South Africa; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D019562:Viral Load
D000942:Antigens, Bacterial; D015703:Antigens, CD; D016207:Cytokines