title: Human CD4(+) effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells.
abstract: 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: Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN), Mexico City, Mexico.
authors: Gabriela
authors: G
authors: González-Pérez
authors: Norma C
authors: NC
authors: Segovia
authors: Amaranta
authors: A
authors: Rivas-Carvalho
authors: Diana P
authors: DP
authors: Reyes
authors: Honorio
authors: H
authors: Torres-Aguilar
authors: Sergio R
authors: SR
authors: Aguilar-Ruiz
authors: Claudine
authors: C
authors: Irles
authors: Gloria
authors: G
authors: Soldevila
authors: Carmen
authors: C
authors: Sánchez-Torres
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010455:Peptides / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D015851:Interleukin-7; D010455:Peptides; D011948:Receptors, Antigen, T-Cell