title: Regulatory T cells suppress T cell activation at the pathologic site of human visceral leishmaniasis.
abstract: Suppression of T cell response is thought to be involved in the pathogenesis of visceral leishmaniasis (VL). Regulatory T cell (Treg) mediated immune-suppression is reported in animal models of Leishmania infection. However, their precise role among human patients still requires pathologic validation. The present study is aimed at understanding the frequency dynamics and function of Treg cells in the blood and bone marrow (BM) of VL patients. The study included 42 parasitologically confirmed patients, 17 healthy contact and 9 normal bone marrow specimens (NBM). We show i) the selective accumulation of Treg cells at one of the disease inflicted site(s), the BM, ii) their in vitro expansion in response to LD antigen and iii) persistence after successful chemotherapy. Results indicate that the Treg cells isolated from BM produces IL-10 and may inhibit T cell activation in IL-10 dependent manner. Moreover, we observed significantly higher levels of IL-10 among drug unresponsive patients, suggesting their critical role in suppression of immunity among VL patients. Our results suggest that IL-10 plays an important role in suppression of host immunity in human VL and possibly determines the efficacy of chemotherapy.
authors.affiliation: Cellular Immunology Division, Department of TII, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Ambak K
authors.initials: AK
authors.lastname: Rai
authors.forename: Chandreshwar P
authors.initials: CP
authors.lastname: Thakur
authors.forename: Amar
authors.initials: A
authors.lastname: Singh
authors.forename: Tulika
authors.initials: T
authors.lastname: Seth
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Pushpendra
authors.initials: P
authors.lastname: Singh
authors.forename: Dipendra K
authors.initials: DK
authors.lastname: Mitra
mesh_terms: D001854:Bone Marrow Cells; D016022:Case-Control Studies; D004358:Drug Therapy; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D016753:Interleukin-10