Document Detail


Donor CD8 T cells and IFN-gamma are critical for sex-based differences in donor CD4 T cell engraftment and lupus-like phenotype in short-term chronic graft-versus-host disease mice.
MedLine Citation:
PMID:  21531893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The transfer of unfractionated DBA/2J (DBA) splenocytes into B6D2F(1) (DBA → F(1)) mice results in greater donor CD4 T cell engraftment in females at day 14 that persists long-term and mediates greater female lupus-like renal disease. Although donor CD8 T cells have no demonstrated role in lupus pathogenesis in this model, we recently observed that depletion of donor CD8 T cells prior to transfer eliminates sex-based differences in renal disease long-term. In this study, we demonstrate that greater day 14 female donor CD4 engraftment is also critically dependent on donor CD8 T cells. Male DBA → F(1) mice exhibit stronger CD8-dependent day 8-10 graft-versus-host (GVH) and counter-regulatory host-versus-graft (HVG) responses, followed by stronger homeostatic contraction (days 10-12). The weaker day 10-12 GVH and HVG in females are followed by persistent donor T cell activation and increasing proliferation, expansion, and cytokine production from days 12 to 14. Lastly, greater female day 14 donor T cell engraftment, activation, and cytokine production were lost with in vivo IFN-γ neutralization from days 6 to 14. We conclude the following: 1) donor CD8 T cells enhance day 10 proliferation of donor CD4 T cells in both sexes; and 2) a weaker GVH/HVG in females allows prolonged survival of donor CD4 and CD8 T cells, allowing persistent activation. These results support the novel conclusion that sex-based differences in suboptimal donor CD8 CTL activation are critical for shaping sex-based differences in donor CD4 T cell engraftment at 2 wk and lupus-like disease long-term.
Authors:
Anthony D Foster; Kateryna Soloviova; Irina Puliaeva; Maksym Puliaiev; Roman Puliaev; Fred Finkelman; Charles S Via
Related Documents :
6389503 - Mutationally altered ribonucleotide reductase from escherichia coli: characterization o...
46253 - Suppression of reaginic antibody formation. ii. the use of adoptive transfer system for...
1386693 - Primed allogeneic reactions to leukocytes and epithelial cells in the bicolor damselfish.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-29
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-20     Completed Date:  2011-08-11     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6238-54     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
CD4-Positive T-Lymphocytes / immunology*,  metabolism
CD8-Positive T-Lymphocytes / immunology*,  metabolism
Cell Proliferation
Cell Transplantation / adverse effects,  methods
Chronic Disease
Cytokines / genetics,  immunology,  metabolism
Female
Flow Cytometry
Graft vs Host Disease / etiology,  immunology*,  metabolism
Host vs Graft Reaction / immunology
Interferon-gamma / genetics,  immunology*,  metabolism
Lupus Erythematosus, Systemic / immunology
Lymphocyte Activation / immunology
Male
Mice
Mice, Inbred DBA
Reverse Transcriptase Polymerase Chain Reaction
Sex Factors
Time Factors
Grant Support
ID/Acronym/Agency:
AI047466/AI/NIAID NIH HHS; R01 AI047466-11/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 82115-62-6/Interferon-gamma
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and...
Next Document:  Endothelin-1 Signaling Promotes Fibrosis In Vitro in a Bronchopulmonary Dysplasia Model by Activatin...