| Autor: |
Rafael Tibúrcio, Gopalan Narendran, Beatriz Barreto-Duarte, Artur T. L. Queiroz, Mariana Araújo-Pereira, Selvaraj Anbalagan, Kaustuv Nayak, Narayanan Ravichandran, Rajasekaran Subramani, Lis R. V. Antonelli, Kumar Satagopan, Komathi Anbalagan, Brian O. Porter, Alan Sher, Soumya Swaminathan, Irini Sereti, Bruno B. Andrade |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology. 13 |
| ISSN: |
1664-3224 |
| Popis: |
BackgroundTuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a clinical aggravation of TB symptoms observed among a fraction of HIV coinfected patients shortly after the start of antiretroviral therapy (ART). Of note, TB-IRIS is characterized by exacerbated inflammation and tissue damage that occurs in response to the elevated production of CD4+ T cell-derived IFN-γ. Nevertheless, the possible participation of CD8+ T cells in TB-IRIS development remains unclear.MethodsWe performed a comprehensive assessment of the composition of CD8+ T cell memory subsets and their association with circulating inflammation-related molecules in TB-HIV coinfected patients initiating ART.ResultsWe found that TB-IRIS individuals display higher frequencies of Antigen-experienced CD8+ T cells during the onset of IRIS and that the levels of these cells positively correlate with baseline mycobacterial smear grade. TB-IRIS individuals exhibited higher frequencies of effector memory and lower percentages of naïve CD8+ T cells than their Non-IRIS counterparts. In both TB-IRIS and Non-IRIS patients, ART commencement was associated with fewer significant correlations among memory CD8+ T cells and cells from other immune compartments. Networks analysis revealed distinct patterns of correlation between each memory subset with inflammatory cytokines suggesting different dynamics of CD8+ T cell memory subsets reconstitution. TB-IRIS patients displayed lower levels of memory cells positive for CXCR3 (a chemokine receptor that plays a role in trafficking activated CD8+ T cells to the tissues) than Non-IRIS individuals before and after ART. Furthermore, we found that CXCR3+ naïve CD8+ T cells were inversely associated with the risk of TB-IRIS development. On the other hand, we noticed that the frequencies of CXCR3+ effector CD8+ T cells were positively associated with the probability of TB-IRIS development.ConclusionOur data suggest that TB-IRIS individuals display a distinct profile of memory CD8+ T cell subsets reconstitution after ART initiation. Moreover, our data point to a differential association between the frequencies of CXCR3+ CD8+ T cells and the risk of TB-IRIS development. Collectively, our findings lend insights into the potential role of memory CD8+ T cells in TB-IRIS pathophysiology. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
