title: Lack of induction of interleukin-2-receptor-alpha in patients with tuberculosis and human immunodeficiency virus co-infection: implications for pathogenesis.
abstract: Since expression of both interleukin-2 (IL-2) and IL-2-receptor-alpha (IL-2R-alpha) by lymphocytes is inhibited by human immunodeficiency virus (HIV) in vitro, we hypothesized that HIV-co-infection among persons with tuberculosis (TB) might impair T-lymphocyte responses to TB via this mechanism. We measured soluble IL-2R-alpha (sIL-2R-alpha), a surrogate marker of T-lymphocyte activation and proliferation, and soluble tumour necrosis factor receptor I (sTNF-RI) in sera from West African patients categorized into 4 groups: those with TB alone (TB+ HIV-, n = 55), CD4-matched groups with TB and HIV co-infection (TB+ HIV+, n = 50) or HIV infection alone (TB- HIV+, n = 35), and patients with neither disease (TB- HIV-, n = 35). The median level of sIL-2R-alpha was markedly greater in the TB+ HIV- group (1580 U/mL) compared to the TB- HIV- (670 U/mL; P < 0.001) and TB- HIV+ (880 U/mL; P < 0.01) groups. More importantly, the median concentration of sIL-2R-alpha was much lower in the TB+ HIV+ group (855 U/mL) compared to the TB+ HIV- group (1580 U/mL; P < 0.01) despite similar levels of sTNF-RI. These results suggest that T-lymphocyte activation in TB patients is impaired by HIV co-infection and, furthermore, this suppressive effect was independent of numerical depletion of CD4 lymphocytes. Impairment to IL-2-signalling might contribute to the profound impact that HIV has had on both the incidence and the clinicopathological manifestations of TB.
authors.affiliation: Tuberculosis/Mycobacteriology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, GA 30333, USA. stevelawn@yahoo.co.uk
authors.forename: S D
authors.initials: SD
authors.lastname: Lawn
authors.forename: D
authors.initials: D
authors.lastname: Rudolph
authors.forename: A
authors.initials: A
authors.lastname: Ackah
authors.forename: D
authors.initials: D
authors.lastname: Coulibaly
authors.forename: S
authors.initials: S
authors.lastname: Wiktor
authors.forename: R B
authors.initials: RB
authors.lastname: Lal
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications* / Q000276:immunology; D000328:Adult; D000818:Animals; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications* / Q000276:immunology
chemical_list: D015375:Receptors, Interleukin-2