HLA-DR Marks Recently Divided Antigen-Specific Effector CD4 T Cells in Active Tuberculosis Patients

• Published in: The Journal of immunology (1950) Vol. 207; no. 2; pp. 523 - 533
• Main Authors: Tippalagama, Rashmi, Singhania, Akul, Dubelko, Paige, Lindestam Arlehamn, Cecilia S, Crinklaw, Austin, Pomaznoy, Mikhail, Seumois, Gregory, deSilva, Aruna D, Premawansa, Sunil, Vidanagama, Dhammika, Gunasena, Bandu, Goonawardhana, N D Suraj, Ariyaratne, Dinuka, Scriba, Thomas J, Gilman, Robert H, Saito, Mayuko, Taplitz, Randy, Vijayanand, Pandurangan, Sette, Alessandro, Peters, Bjoern, Burel, Julie G
• Format: Journal Article
• Language: English
• Published: United States 15-07-2021
• Subjects: CD4-Positive T-Lymphocytes - immunology; HLA-DR Antigens; Humans; Mycobacterium tuberculosis; Tuberculosis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2100011

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
-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
Ag-specific CD4 T cells. We tested and confirmed that HLA-DR is a marker of recently divided CD4 T cells upon
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.