Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes

Frontiers in Immunology

Gustavo Reyes-Terán¹  Ning Jiang²  Philip L. De Jager³  Laura F. Su⁴  Daniel Del Alcazar⁴  Yuria Ablanedo-Terrazas⁵  Perla M. Del Río-Estrada⁵  Chenfeng He⁷  Ke-Yue Ma⁹  Michael J. Malone⁹  Ben S. Wendel^1,10  David B. Weiner^1,11 

[1] 0Comisión Coordinadora de Institutos Nacional de Salud y Hospitales de Alta Especialidad, Secretaría de Salud, Ciudad de México, Mexico;1Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States;Columbia University Medical Center, Center for Translational and Computational Neuroimmunology, New York, NY, United States;Corporal Michael J Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States;Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, Mexico;Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States;Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, United States;Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA, United States;Interdisciplinary Life Sciences Graduate Program, University of Texas at Austin, Austin, TX, United States;McKetta Department of Chemical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, United States;Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA, United States;

关键词: CXCR3;    follicular-helper T cells (TFH);    TCR repertoire;    RNA-seq;    HIV;   

DOI  :  10.3389/fimmu.2022.859070

来源: DOAJ

【 摘 要 】

Follicular-helper T cells (TFH) are an essential arm of the adaptive immune system. Although TFH were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex and functionally plastic cell type. Due to a lack sample availability, however, many studies have been limited to characterizing TFH in mice or non-canonical tissue types, such as peripheral blood. Such constraints have resulted in a limited, and sometimes contradictory, understanding of this fundamental cell type. One subset of TFH receiving attention in chronic infection are CXCR3-expressing TFH cells (CXCR3+TFH) due to their abnormal accumulation in secondary lymphoid tissues. Their function and clonal relationship with other TFH subsets in lymphoid tissues during infection, however, remains largely unclear. We thus systematically investigated this and other subsets of TFH within untreated HIV-infected human lymph nodes using Mass CyTOF and a combination of RNA and TCR repertoire sequencing. We show an inflation of the CXCR3+TFH compartment during HIV infection that correlates with a lower HIV burden. Deeper analysis into this population revealed a functional shift of CXCR3+TFH away from germinal center TFH (GC-TFH), including the altered expression of several important transcription factors and cytokines. CXCR3+TFH also upregulated cell migration transcriptional programs and were clonally related to peripheral TFH populations. In combination, these data suggest that CXCR3+TFH have a greater tendency to enter circulation than their CXCR3- counterparts, potentially functioning through distinct modalities that may lead to enhanced defense.

【 授权许可】

Unknown