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Human CD4+ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells

Cellular & Molecular Immunology volume 10, pages 261–274 (2013)Cite this article

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.

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Acknowledgements

We gratefully acknowledge the generosity of the blood donors and the support of the Blood Bank staff at Centro Medico Nacional La Raza Hospital (Mexico City) in providing the blood samples. We also thank Victor H. Rosales for help with flow cytometry, Dr. Nicolás Villegas for his aid in caspase-3 detection, Julio C. Ramírez for technical assistance, and Ms. Ninfa Arreola for her aid in the preparation of the manuscript. This work was supported by grants to C.S.T. from CONACYT (no. 81112 and 140980).

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Authors and Affiliations

  1. Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN), Mexico City, Mexico

    Gabriela González-Pérez, Norma C Segovia, Amaranta Rivas-Carvalho, Diana P Reyes, Honorio Torres-Aguilar, Sergio R Aguilar-Ruiz & Carmen Sánchez-Torres

  2. Department of Physiology, Facultad de Medicina, Mexico City, Mexico

    Claudine Irles

  3. Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico

    Gloria Soldevila

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Correspondence to Carmen Sánchez-Torres.

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González-Pérez, G., Segovia, N., Rivas-Carvalho, A. et al. Human CD4+ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells. Cell Mol Immunol 10, 261–274 (2013). https://doi.org/10.1038/cmi.2012.71

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