title: Role of CD8(+) T cells in protection against Leishmania donovani infection in healed Visceral Leishmaniasis individuals.
abstract: BACKGROUND
  Majority of individuals with history of visceral leishmaniasis (VL) exhibit strong immunity to re-infection, however, the mechanism of resistance is poorly understood. It is unclear whether CD8(+) T cells contribute to protection against Leishmania donovani infection through cytotoxic activity. The present study aims to evaluate immunological mechanism associated with resistance to the disease in healed VL (HVL) individuals and further, the contribution of CD8(+) T cells in the protective immunity.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) from VL, HVL and naive groups were exposed in vitro to total soluble Leishmania antigen (TSLA) from L. donovani. The proliferation index was determined by ELISA based lymphoproliferative assay. Cytokines and granzyme B levels were measured by CBA. Activated T-cell populations were estimated using flow cytometry.
  
  
  RESULTS
  We observed significantly higher lymphoproliferation, cytokines and granzyme B levels in HVL group compared to naive or VL group. More strikingly, we found a strong association (rs = 0.895, P < 0.0001) between proliferation index (PI) and granzyme B level, with a significant proportion of activated CD8(+) T cells in HVL group.
  
  
  CONCLUSIONS
  Leishmania immune group (HVL) exhibited durable and strong cellular immune response to TSLA in terms of lymphoproliferation as well as production of Th1 cytokines and granzyme B. Additionally, the elevated level of activated CD8(+) T cells and stimulation of cytotoxic activity through granzyme B production, indicated a possible role of CD8(+) T cells in resistance to L. donovani infection in the HVL group.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kaushal
authors.forename: Rachel
authors.initials: R
authors.lastname: Bras-Gonçalves
authors.forename: Narender Singh
authors.initials: NS
authors.lastname: Negi
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Lemesre
authors.forename: Gérard
authors.initials: G
authors.lastname: Papierok
authors.affiliation: National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India. salotrap@icmr.org.in.
authors.forename: Poonam
authors.initials: P
authors.lastname: Salotra
mesh_terms: D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008213:Lymphocyte Activation; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016207:Cytokines; C509213:GZMB protein, human; D053804:Granzymes