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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Parasite Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1475146
This article is part of the Research Topic Interactions among Immune Cells in Leishmaniasis: Exploring Markers, Enzymes and Cytokines View all articles

Lesional senescent CD4 + T cells mediate bystander cytolysis and contribute to the skin pathology of human cutaneous leishmaniasis

Provisionally accepted
Luciana Covre Luciana Covre 1Carlos Henrique Fantecelle Carlos Henrique Fantecelle 1Renan Garcia Renan Garcia 1Paola Oliveira Paola Oliveira 1Isabela Sarmento Isabela Sarmento 1Celio G. Freire-de-Lima Celio G. Freire-de-Lima 2Debora Decote-Ricardo Debora Decote-Ricardo 3Herbert L. de Matos Guedes Herbert L. de Matos Guedes 2Alessandra M. da Fonseca-Martins Alessandra M. da Fonseca-Martins 2Lucas P. Carvalho Lucas P. Carvalho 4Edgar M. Carvalho Edgar M. Carvalho 4David M. Mosser David M. Mosser 5Aloisio Falqueto Aloisio Falqueto 1Arne A. Akbar Arne A. Akbar 6Daniel C. Gomes Daniel C. Gomes 1*
  • 1 Federal University of Espirito Santo, Vitória, Brazil
  • 2 Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
  • 3 Federal Rural University of Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil
  • 4 Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
  • 5 University of Maryland, Baltimore, Maryland, United States
  • 6 University College London, London, England, United Kingdom

The final, formatted version of the article will be published soon.

    Cytotoxic activity is a hallmark of the immunopathogenesis in human cutaneous leishmaniasis (CL). In this study, we identified accumulation of CD4 + granzyme B producing T cells with increased cytotoxic capacity in CL lesions. These cells showed enhanced expression of activating NK receptors (NKG2D and NKG2C), diminished expression of inhibitory NKG2A, along with the upregulation of the senescence marker CD57. Notably, CD4 + T cells freshly isolated from CL lesions demonstrated remarkable capacity to mediate NL-like bystander cytolysis. Phenotypic analyses revealed that lesional CD4 + T cells are mainly composed of latedifferentiated effector (CD27-CD45RA-) and terminally differentiated (senescent) TEMRA (CD27-CD45RA+) subsets. Interestingly, the TEMRA CD4 + T cells exhibited higher expression of granzyme B and CD107a. Collectively, our results provide the first evidence that senescent cytotoxic CD4 + T cells may support the skin pathology of human cutaneous leishmaniasis and, together with our previous findings, support the notion that multiple subsets of cytotoxic senescent cells may be involved in inducing the skin lesions in these patients.

    Keywords: CD4-CTL, cutaneous leishmaniasis, Leishmania braziliensis, Senescent cells, bystander cytotoxicity

    Received: 02 Aug 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Covre, Fantecelle, Garcia, Oliveira, Sarmento, Freire-de-Lima, Decote-Ricardo, de Matos Guedes, da Fonseca-Martins, Carvalho, Carvalho, Mosser, Falqueto, Akbar and Gomes. 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) or licensor 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: Daniel C. Gomes, Federal University of Espirito Santo, Vitória, Brazil

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