PMID- 25275531
OWN - NLM
STAT- MEDLINE
DCOM- 20160208
LR  - 20211021
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 8
IP  - 10
DP  - 2014 Oct
TI  - Leishmania specific CD4 T cells release IFNgamma that limits parasite replication in 
      patients with visceral leishmaniasis.
PG  - e3198
LID - 10.1371/journal.pntd.0003198 [doi]
LID - e3198
AB  - Visceral leishmaniasis (VL) is associated with increased circulating levels of 
      multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNgamma, and 
      TNFalpha, and elevated expression of IFNgamma 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 IFNgamma, 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 
      IFNgamma found to be released by cells from VL patients. CD4+ T cells were found to 
      be crucial for and the main source of the IFNgamma 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 IFNgamma response. The 
      IFNgamma 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 IFNgamma in ex-vivo splenic aspirate cultures demonstrated 
      that despite the progressive nature of their disease, the endogenous IFNgamma 
      produced in patients with active VL serves to limit parasite growth.
FAU - Kumar, Rajiv
AU  - Kumar R
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India; Department of Immunology and Infection, Queensland Institute of Medical 
      Research, Herston, Queensland, Australia.
FAU - Singh, Neetu
AU  - Singh N
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India.
FAU - Gautam, Shalini
AU  - Gautam S
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India.
FAU - Singh, Om Prakash
AU  - Singh OP
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India.
FAU - Gidwani, Kamlesh
AU  - Gidwani K
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India; Department of Biotechnology, University of Turku, Turku, Finland.
FAU - Rai, Madhukar
AU  - Rai M
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India.
FAU - Sacks, David
AU  - Sacks D
AD  - National Institute of Allergy and Infectious Diseases, National Institutes of 
      Health, Bethesda, Maryland, United States of America.
FAU - Sundar, Shyam
AU  - Sundar S
AD  - Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 
      India.
FAU - Nylen, Susanne
AU  - Nylen S
AD  - Karolinska Institutet, Department of Microbiology Tumor and Cell Biology, 
      Stockholm, Sweden.
LA  - eng
GR  - P50 AI074321/AI/NIAID NIH HHS/United States
GR  - U19 AI074321/AI/NIAID NIH HHS/United States
GR  - 2P50AI074321/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141002
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - CD4-Positive T-Lymphocytes/*metabolism
MH  - Cell Division
MH  - Child
MH  - Female
MH  - Humans
MH  - Interferon-gamma/genetics/*metabolism
MH  - Leishmania/*immunology
MH  - Leishmaniasis, Visceral/*immunology/parasitology
MH  - Male
MH  - Middle Aged
MH  - Spleen/cytology
MH  - Young Adult
PMC - PMC4183461
COIS- The authors have declared that no competing interests exist.
EDAT- 2014/10/03 06:00
MHDA- 2016/02/09 06:00
PMCR- 2014/10/02
CRDT- 2014/10/03 06:00
PHST- 2014/03/14 00:00 [received]
PHST- 2014/08/18 00:00 [accepted]
PHST- 2014/10/03 06:00 [entrez]
PHST- 2014/10/03 06:00 [pubmed]
PHST- 2016/02/09 06:00 [medline]
PHST- 2014/10/02 00:00 [pmc-release]
AID - PNTD-D-14-00448 [pii]
AID - 10.1371/journal.pntd.0003198 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2014 Oct 2;8(10):e3198. doi: 10.1371/journal.pntd.0003198. 
      eCollection 2014 Oct.