Document Detail


Human CD4(+) effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells.
MedLine Citation:
PMID:  23454917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The peripheral repertoire of CD4(+) T lymphocytes contains autoreactive cells that remain tolerant through several mechanisms. However, nonspecific CD4(+) T cells can be activated in physiological conditions as in the course of an ongoing immune response, and their outcome is not yet fully understood. Here, we investigate the fate of human naive CD4(+) lymphocytes activated by dendritic cells (DCs) presenting endogenous self-peptides in comparison with lymphocytes involved in alloresponses. We generated memory cells (Tmem) from primary effectors activated with mature autologous DCs plus interleukin (IL)-2 (Tmauto), simulating the circumstances of an active immune response, or allogeneic DCs (Tmallo). Tmem were generated from effector cells that were rested in the absence of antigenic stimuli, with or without IL-7. Tmem were less activated than effectors (demonstrated by CD25 downregulation) particularly with IL-7, suggesting that this cytokine may favour the transition to quiescence. Tmauto and Tmallo showed an effector memory phenotype, and responded similarly to polyclonal and antigen-specific stimuli. Biochemically, IL-7-treated Tmallo were closely related to conventional memory lymphocytes based on Erk-1/2 activation, whereas Tmauto were more similar to effectors. Autologous effectors exhibited lower responses to IL-7 than allogeneic cells, which were reflected in their reduced proliferation and higher cell death. This was not related to IL-7 receptor expression but rather to signalling deficiencies, according to STAT5 activation These results suggest that ineffective responses to IL-7 could impair the transition to memory cells of naive CD4(+) T lymphocytes recognizing self-peptides in the setting of strong costimulation.
Authors:
Gabriela González-Pérez; Norma C Segovia; Amaranta Rivas-Carvalho; Diana P Reyes; Honorio Torres-Aguilar; Sergio R Aguilar-Ruiz; Claudine Irles; Gloria Soldevila; Carmen Sánchez-Torres
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-04
Journal Detail:
Title:  Cellular & molecular immunology     Volume:  10     ISSN:  2042-0226     ISO Abbreviation:  Cell. Mol. Immunol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-06     Completed Date:  2014-03-21     Revised Date:  2014-08-19    
Medline Journal Info:
Nlm Unique ID:  101242872     Medline TA:  Cell Mol Immunol     Country:  China    
Other Details:
Languages:  eng     Pagination:  261-74     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
CD4-Positive T-Lymphocytes / cytology*,  drug effects,  immunology*
Cell Proliferation / drug effects
Cell Separation
Cell Survival / drug effects,  immunology
Humans
Immunologic Memory / drug effects*
Immunophenotyping
Interleukin-7 / pharmacology*
Lymphocyte Activation / drug effects
Peptides / metabolism*
Receptors, Antigen, T-Cell / metabolism*
Signal Transduction / drug effects,  immunology
Chemical
Reg. No./Substance:
0/Interleukin-7; 0/Peptides; 0/Receptors, Antigen, T-Cell
Comments/Corrections

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