Lower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients

Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. in this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. the volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M.leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.0070.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.0320.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.0300.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-? after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M.leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers.National Institutes of HealthFogarty International CenterFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Brazilian Ministry of Science and TechnologyNew York Community TrustUniv São Paulo, Lab Invest Med 60, Div Clin Immunol & Allergy, BR-01246903 São Paulo, BrazilUniv Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Expt Med, San Francisco, CA USAUniversidade Federal de São Paulo, São Paulo, BrazilFed Univ Para, BR-66059 Belem, Para, BrazilShire Human Genet Therapies, Lexington, MA USAUniversidade Federal de São Paulo, São Paulo, BrazilNational Institutes of Health: R01-AI52731National Institutes of Health: AI060379Fogarty International Center: D43 TW00003FAPESP: 04/15856-9/KallasFAPESP: 2010/05845-0/KallasBrazilian Ministry of Science and Technology: 484230/2011-5Web of Scienc