Lack of induction of interleukin-2-receptor-alpha in patients with tuberculosis and human immunodeficiency virus co-infection: implications for pathogenesis.


Lawn, SD; Rudolph, D; Ackah, A; Coulibaly, D; Wiktor, S; Lal, RB; (2001) Lack of induction of interleukin-2-receptor-alpha in patients with tuberculosis and human immunodeficiency virus co-infection: implications for pathogenesis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 95 (4). pp. 449-52. ISSN 0035-9203 DOI: https://doi.org/10.1016/S0035-9203(01)90212-3

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 11579894
Web of Science ID: 171336900025
URI: http://researchonline.lshtm.ac.uk/id/eprint/13018

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