Impact Factor 6.429

The 5th most cited journal in Immunology

This article is part of the Research Topic

The Aging Immune System and Health

Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.00339

Influence of inflammation in the process of T lymphocyte differentiation: proliferative, metabolic and oxidative changes

  • 1Immunology, Central University Hospital of Asturias, Spain
  • 2Morfologia y Biologia Celular, Universidad de Oviedo, Spain
  • 3Faculta de Ciencias de la Salud, Universidad Autónoma de Chile, Chile

T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen (chronic antigens). This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form. This process plays a fundamental role in amplifying the activating signals on T lymphocytes and directing their clonal proliferation. The mechanisms that control cell growth are high levels of telomerase activity and maintenance of telomeric length that are far superior to other cell types, as well as metabolic adaptation and redox control. Large numbers of highly differentiated memory cells are accumulated in the immunological niches where they will contribute in a significant way to increase the levels of inflammatory mediators that will perpetuate the new state at the systemic level. These levels of inflammation greatly influence the process of T lymphocytes differentiation from naïve T lymphocyte, even before, until the arrival of exhaustion or cell death. The changes observed during lymphocyte differentiation are correlated with changes in cellular metabolism and these in turn are influenced by the inflammatory state of the environment where the cell is located. Reactive oxygen species (ROS) exert a dual action in the population of T lymphocytes. Exposure to high levels of ROS decreases the capacity of activation and T lymphocyte proliferation; however, intermediate levels of oxidation are necessary for the lymphocyte activation, differentiation and effector functions. In conclusion, we can affirm that the inflammatory levels in the environment greatly influence the differentiation and activity of T lymphocyte populations. However, little is known about the mechanisms involved in these processes. The elucidation of these mechanisms would be of great help in the advance of improvements in pathologies with a large inflammatory base such as rheumatoid arthritis, intestinal inflammatory diseases, several infectious diseases and even, cancerous processes.

Keywords: Inflammation, T lymphocytes, differentiation, metabolic reprogramming, exhaustion, redox balance

Received: 06 Nov 2017; Accepted: 06 Feb 2018.

Edited by:

Rafael Solana, Universidad de Córdoba, Spain

Reviewed by:

Shi Yue, University of Southern California, United States
Sara Ferrando-Martinez, MedImmune, United States
Carmen Vida, Complutense University of Madrid, Spain  

Copyright: © 2018 Moro-García, Mayo, Sainz and Alonso-Arias. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Rosa M. Sainz, Universidad de Oviedo, Morfologia y Biologia Celular, Julian Claveria, 6, Oviedo, Julian Claveria, 6, Facultad de Medicina, Oviedo, 33006, Asturias, Spain, sainzrosa@uniovi.es
Dr. Rebeca Alonso-Arias, Central University Hospital of Asturias, Immunology, Av. Roma, s/n,, Oviedo, 33011 s, Asturia, Spain, ralonsoarias@hotmail.es