HLA-DR marks recently divided antigen-specific effector CD4 T cells in active tuberculosis patients

Rashmi Tippalagama, Akul Singhania, Paige Dubelko, Cecilia S. Lindestam Arlehamn, Austin Crinklaw, Mikhail Pomaznoy, Gregory Seumois, Aruna D. deSilva, Sunil Premawansa, Dhammika Vidanagama, Bandu Gunasena, N. D.Suraj Goonawardhana, Dinuka Ariyaratne, Thomas J. Scriba, Robert H. Gilman, Mayuko Saito, Randy Taplitz, Pandurangan Vijayanand, Alessandro Sette, Bjoern PetersJulie G. Burel

Research output: Contribution to journalArticlepeer-review

Abstract

Upon Ag encounter, T cells can rapidly divide and form an effector population, which plays an important role in fighting acute infections. In humans, little is known about the molecular markers that distinguish such effector cells from other T cell populations. To address this, we investigated the molecular profile of T cells present in individuals with active tuberculosis (ATB), where we expect Ag encounter and expansion of effector cells to occur at higher frequency in contrast to Mycobacterium tuberculosis-sensitized healthy IGRA+ individuals. We found that the frequency of HLA-DR+ cells was increased in circulating CD4 T cells of ATB patients, and was dominantly expressed in M. tuberculosis Ag-specific CD4 T cells. We tested and confirmed that HLA-DR is a marker of recently divided CD4 T cells upon M. tuberculosis Ag exposure using an in vitro model examining the response of resting memory T cells from healthy IGRA+ to Ags. Thus, HLA-DR marks a CD4 T cell population that can be directly detected ex vivo in human peripheral blood, whose frequency is increased during ATB disease and contains recently divided Ag-specific effector T cells. These findings will facilitate the monitoring and study of disease-specific effector T cell responses in the context of ATB and other infections.

Original languageEnglish
Pages (from-to)523-533
Number of pages11
JournalJournal of Immunology
Volume207
Issue number2
DOIs
Publication statusPublished - 2021 Jul 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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