title: Leishmania specific CD4 T cells release IFNγ that limits parasite replication in patients with visceral leishmaniasis.
abstract: Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA) is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB) cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA)-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR) driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth.
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; Department of Immunology and Infection, Queensland Institute of Medical Research, Herston, Queensland, Australia.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Singh
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; Department of Biotechnology, University of Turku, Turku, Finland.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Gidwani
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Rai
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Sacks
authors.affiliation: Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Karolinska Institutet, Department of Microbiology Tumor and Cell Biology, Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylén
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002455:Cell Division; D002648:Child; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007891:Leishmania / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D013154:Spleen / Q000166:cytology; D055815:Young Adult
chemical_list: D007371:Interferon-gamma