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    
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.
Anthony D Foster; Kateryna Soloviova; Irina Puliaeva; Maksym Puliaiev; Roman Puliaev; Fred Finkelman; Charles S Via
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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:  2014-09-10    
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    
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MeSH Terms
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
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
Mice, Inbred DBA
Reverse Transcriptase Polymerase Chain Reaction
Sex Factors
Time Factors
Grant Support
Reg. No./Substance:
0/Cytokines; 82115-62-6/Interferon-gamma

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