Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19

Naoki Kaneko, Julie Boucau, Hsiao Hsuan Kuo, Cory Perugino, Vinay S. Mahajan, Jocelyn R. Farmer, Hang Liu, Thomas J. Diefenbach, Alicja Piechocka-Trocha, Kristina Lefteri, Michael T. Waring, Katherine R. Premo, Bruce D. Walker, Jonathan Z. Li, Gaurav Gaiha, Xu G. Yu, Mathias Lichterfeld, Robert F. Padera, Shiv Pillai

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21 Citations (Scopus)


Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping the field build a picture of the mechanisms that drive severe lung disease. Approaches employed to date have not revealed information on lung parenchymal T cell subsets in severe COVID-19. Therefore, we sought to examine early and late T cell subset alterations in the lungs and draining lymph nodes in severe COVID-19 using a rapid autopsy protocol and quantitative imaging approaches. Here, we have established that cytotoxic CD4+ T cells (CD4 + CTLs) increase in the lungs, draining lymph nodes and blood as COVID-19 progresses. CD4 + CTLs are prominently expanded in the lung parenchyma in severe COVID-19. In contrast CD8+ T cells are not prominent, exhibit increased PD-1 expression, and no obvious increase is seen in the number of Granzyme B+ CD8+ T cells in the lung parenchyma in severe COVID-19. Based on quantitative evidence for re-activation in the lung milieu, CD4 + CTLs may be as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.

Original languageEnglish
Article number108991
JournalClinical Immunology
Publication statusPublished - Apr 2022

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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