Document Detail


Differential requirement of RasGRP1 for γδ T cell development and activation.
MedLine Citation:
PMID:  22623331     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
γδ T (γδT) cells belong to a distinct T cell lineage that performs immune functions different from αβ T (αβT) cells. Previous studies established that Erk1/2 MAPKs are critical for positive selection of αβT cells. Additional evidence suggests that increased Erk1/2 activity promotes γδT cell generation. RasGRP1, a guanine nucleotide-releasing factor for Ras, plays an important role in positive selection of αβT cells by activating the Ras-Erk1/2 pathway. In this article, we demonstrate that RasGRP1 is critical for TCR-induced Erk1/2 activation in γδT cells, but it exerts different roles for γδT cell generation and activation. Deficiency of RasGRP1 does not obviously affect γδT cell numbers in the thymus, but it leads to increased γδT cells, particularly CD4(-)CD8(+) γδT cells, in the peripheral lymphoid organs. The virtually unhindered γδT cell development in the RasGRP1(-/-) thymus proved to be cell intrinsic, whereas the increase in CD8(+) γδT cells is caused by non-cell-intrinsic mechanisms. Our data provide genetic evidence that decreased Erk1/2 activation in the absence of RasGRP1 is compatible with γδT cell generation. Although RasGRP1 is dispensable for γδT cell generation, RasGRP1-deficient γδT cells are defective in proliferation following TCR stimulation. Additionally, RasGRP1-deficient γδT cells are impaired to produce IL-17 but not IFNγ. Together, these observations revealed that RasGRP1 plays differential roles for γδ and αβ T cell development but is critical for γδT cell proliferation and production of IL-17.
Authors:
Yong Chen; Xinxin Ci; Balachandra Gorentla; Sarah A Sullivan; James C Stone; Weiguo Zhang; Pablo Pereira; Jianxin Lu; Xiao-Ping Zhong
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-23
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  189     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-22     Completed Date:  2012-09-07     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  61-71     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / genetics,  immunology*
Cell Proliferation
Guanine Nucleotide Exchange Factors / deficiency,  genetics,  physiology*
Interleukin-17 / biosynthesis
Lymphocyte Activation / genetics,  immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Organ Specificity / genetics,  immunology
Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
Spleen / cytology,  immunology,  metabolism
T-Lymphocyte Subsets / cytology*,  immunology*,  metabolism
Thymocytes / cytology,  immunology,  metabolism
Grant Support
ID/Acronym/Agency:
R01 AI076357/AI/NIAID NIH HHS; R01 AI079088/AI/NIAID NIH HHS; R01AI076357/AI/NIAID NIH HHS; R01AI079088/AI/NIAID NIH HHS; R21 AI079873/AI/NIAID NIH HHS; R21AI079873/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Guanine Nucleotide Exchange Factors; 0/Interleukin-17; 0/Rasgrp1 protein, mouse; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Receptors, Antigen, T-Cell, gamma-delta
Comments/Corrections

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