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1.
Nat Commun ; 11(1): 6357, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311473

RESUMO

The prevailing 'division of labor' concept in cellular immunity is that CD8+ T cells primarily utilize cytotoxic functions to kill target cells, while CD4+ T cells exert helper/inducer functions. Multiple subsets of CD4+ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8+ memory T-cell subsets exist, characterized by identical chemokine receptor expression signatures and controlled by similar generic programs. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17 + 1 cells, express IL-6R but not SLAMF7, completely lack cytotoxicity and instead display helper functions including CD40L expression. CD8+ helper T cells exhibit a unique TCR repertoire, express genes related to skin resident memory T cells (TRM) and are altered in the inflammatory skin disease psoriasis. Our findings reveal that the conventional view of CD4+ and CD8+ T cell capabilities and functions in human health and disease needs to be revised.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Receptores de Interleucina-6/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Ligante de CD40/metabolismo , Diferenciação Celular , Quimiocinas/metabolismo , Citocinas/metabolismo , Citotoxicidade Imunológica , Expressão Gênica , Humanos , Imunidade Celular , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina-6/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Pele/imunologia , Subpopulações de Linfócitos T/imunologia
2.
PLoS One ; 12(7): e0181161, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28700738

RESUMO

Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluate the kinetics of γδ T cells after vaccination with the trivalent 2011/2012 northern hemisphere seasonal influenza vaccine. We applied multi-parametric flow cytometry to a cohort of 21 young (19-30 years) and 23 elderly (53-67 years) healthy individuals. Activated and proliferating γδ T cells, as identified by CD38 and Ki67 expression, were quantified on the days 0, 3, 7, 10, 14, 17, and 21. We observed a significantly lower number of activated and proliferating γδ T cells at baseline and following vaccination in elderly as compared to young individuals. The kinetics changes of activated γδ T cells were much stronger in the young, while corresponding changes in the elderly occurred slower. In addition, we observed an association between day 21 HAI titers of influenza A and the frequencies of Ki67+ γδ T cells at day 7 in the young. In conclusion, aging induces alterations of the γδ T cell response that might have negative implications for vaccination efficacy.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Linfócitos T/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Idoso , Envelhecimento/fisiologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Cinética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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