HIV-1 infection alters CD4+memory T-cell phenotype at the site of disease in extrapulmonary tuberculosis

Autor: Katalin A. Wilkinson, Mpiko Ntsekhe, James R Russell, Armin Deffur, Bongani M. Mayosi, Robert J. Wilkinson, Kerryn Matthews, Thomas J. Scriba, Faisal F. Syed, Willem A. Hanekom, Kemi Tibazarwa
Rok vydání: 2011
Předmět:
Zdroj: European Journal of Immunology. 42:147-157
ISSN: 0014-2980
DOI: 10.1002/eji.201141927
Popis: HIV-1-infected people have an increased risk of developing extrapulmonary tuberculosis (TB), the immunopathogenesis of which is poorly understood. Here, we conducted a detailed immunological analysis of human pericardial TB, to determine the effect of HIV-1 co-infection on the phenotype of Mycobacterium tuberculosis (MTB)-specific memory T cells and the role of polyfunctional T cells at the disease site, using cells from pericardial fluid and blood of 74 patients with (n=50) and without (n=24) HIV-1 co-infection. The MTB antigen-induced IFN-γ response was elevated at the disease site, irrespective of HIV-1 status or antigenic stimulant. However, the IFN-γ ELISpot showed no clear evidence of increased numbers of antigen-specific cells at the disease site except for ESAT-6 in HIV-1 uninfected individuals (p=0.009). Flow cytometric analysis showed that CD4+ memory T cells in the pericardial fluid of HIV-1-infected patients were of a less differentiated phenotype, with the presence of polyfunctional CD4+ T cells expressing TNF, IL-2 and IFN-γ. These results indicate that HIV-1 infection results in altered phenotype and function of MTB-specific CD4+ T cells at the disease site, which may contribute to the increased risk of developing TB at all stages of HIV-1 infection.
Databáze: OpenAIRE
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