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

✍ Scribed by Kerryn Matthews; Mpiko Ntsekhe; Faisal Syed; Thomas Scriba; James Russell; Kemi Tibazarwa; Armin Deffur; Willem Hanekom; Bongani M. Mayosi; Robert J. Wilkinson; Katalin A. Wilkinson

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 324 KB
• Volume: 42
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.201141927

✦ Synopsis

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.