| Autor: |
Roy Chowdhury, Roshni, Valainis, John R., Dubey, Megha, von Boehmer, Lotta, Sola, Elsa, Wilhelmy, Julie, Guo, Jing, Kask, Oliver, Ohanyan, Mane, Sun, Meng, Huang, Huang, Huang, Xianxi, Nguyen, Patricia K., Scriba, Thomas J., Davis, Mark M., Bendall, Sean C., Chien, Yueh-hsiu |
| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 81, p1-16, 16p |
| Abstrakt: |
The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in acute Mycobacterium tuberculosis (Mtb) infection is well characterized, but their response during persistent Mtb infection is not well understood, even though most infections with Mtb manifest as a chronic, clinically asymptomatic state. Here, we analyze peripheral blood γδ T cells from a South African adolescent cohort and show that a unique CD8+ γδ T cell subset with features of "memory inflation" expands in chronic Mtb infection. These cells are hyporesponsive to T cell receptor (TCR)–mediated signaling but, like NK cells, can mount robust CD16-mediated cytotoxic responses. These CD8+ γδ T cells comprise a highly focused TCR repertoire, with clonotypes that are Mycobacterium specific but not phosphoantigen reactive. Using multiparametric single-cell pseudo-time trajectory analysis, we identified the differentiation paths that these CD8+ γδ T cells follow to develop into effectors in this infection state. Last, we found that circulating CD8+ γδ T cells also expand in other chronic inflammatory conditions, including cardiovascular disease and cancer, suggesting that persistent antigenic exposure may drive similar γδ T cell effector programs and differentiation fates. A chronic identity shift: Acute versus chronic stage-specific γδ T cell responses to the same infection are not well-defined. Active Mycobacterium tuberculosis (Mtb) infection is known to induce phosphoantigen-reactive effector γδ T cells. In this study, Roy Chowdhury et al. studied γδ T cells in a cohort of South African adolescents with persistent or controlled Mtb infection. They identified an expanded population of CD8+ γδ T cells with NK-cell–like features. These cells had a focused TCR repertoire and were reactive to Mtb antigens. They were hyporesponsive to TCR-mediated activation but exhibited effective cytotoxic responses downstream of CD16. CD8+ γδ T cells were also expanded in other chronic inflammatory conditions with diverse etiologies. Together these findings identify CD8+ γδ T cells as a common feature of chronic infection and inflammation in humans. —HMI [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
