Inclusion and exclusion of CD4+ and CD8+ T cells into the germinal centre during health and HIV-1 disease
The activation and differentiation of B cells in germinal centers (GCs) plays an essential role in protective immunity but is also linked to autoimmunity and lymphoma. CD4+ follicular helper T cells thereby “help” B cell maturation in germinal centers. Cytolytic CD8⁺ T cells (CTLs), in contrast, were long-time assumed to be excluded from GCs. Thus, CTLs were not linked to the process of activation and differentiation of B cells so far. In people living with HIV-1 infection (PLWH) CXCR5+ “follicular” CTLs have recently been found in the GC attacking HIV-infected CD4+ follicular helper T cells. Given the general importance of GCs for B cell immunity also in healthy individuals, this project aims at elucidating general rules of GC inclusion or exclusion of CD4+ and CD8+ T cells. To this end, we will analyze PLWH and healthy donors after vaccination, and profile T and B cell immunity in human lymph nodes and paired peripheral blood samples by single-cell profiling (flow cytometry and RNA sequencing) as well as spatial methodologies (conventional histology and spatial transcriptomics). The ultimate aim of the project is to unravel the role of lymph nodes as “sanctuaries” during HIV-1 infection, and gain insights into general GC biology.
