| Autor: |
Collins, David R., Hitschfel, Julia, Urbach, Jonathan M., Mylvaganam, Geetha H., Ly, Ngoc L., Arshad, Umar, Racenet, Zachary J., Yanez, Adrienne G., Diefenbach, Thomas J., Walker, Bruce D. |
| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 83, p1-17, 17p |
| Abstrakt: |
Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s. Spontaneous controller secrets revealed: Individuals who spontaneously control HIV infection without antiviral treatment have provided critical insights into natural HIV immunity. Collins and Hitschfel et al. studied CD8+ T cells in spontaneous controllers of HIV to better understand mechanisms involved in HIV control. They examined the phenotypic, transcriptomic, and functional features, spatial localization, and clonotypic compartmentalization of peripheral and lymph node (LN)–resident CD8+ T cells. Controllers displayed antigen-specific proliferation and cytolytic potential that was different from noncontrollers. Within controllers, TCR analysis confirmed shared clonotypes detected in periphery and LN, although LN CD8+ T cells had a gene signature enriched in effector and inflammatory chemotaxis functions. CXCR5+ follicular CD8+ T cells enriched in controllers expressed cytolytic effectors near HIV RNA foci in germinal centers. These findings provide insight into how HIV-specific lymphoid cells mediate control of HIV in LNs. —CNF [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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