Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function

By P. Schaerli, K. Willimann, A. Lang, M. Lipp, P. Loetscher, B. Moser. Journal of Experimental Medicine, 2000

1,352 citations recorded by the source corpus.

Leukocyte traffic through secondary lymphoid tissues is finely tuned by chemokines. We have studied the functional properties of a human T cell subset marked by the expression of CXC chemokine receptor 5 (CXCR5). Memory but not naive T cells from tonsils are CXCR5+ and migrate in response to the B cell–attracting chemokine 1 (BCA-1), which is selectively expressed by reticular cells and blood vessels within B cell follicles. Tonsillar CXCR5+ T cells do not respond to other chemokines present in secondary lymphoid tissues, including secondary lymphoid tissue chemokine (SLC), EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell–derived factor 1 (SDF-1). The involvement of tonsillar CXCR5+ T cells in humoral immune responses is suggested by their localization in the mantle and light zone germinal centers of B cell follicles and by the concomitant expression of activation and costimulatory markers, including CD69, HLA-DR, and inducible costimulator (ICOS). Peripheral blood CXCR5+ T cells also belong to the CD4+ memory T cell subset but, in contrast to tonsillar cells, are in a resting state and migrate weakly to chemokines. CXCR5+ T cells are very inefficient in the production of cytokines but potently induce antibody production during coculture with B cells. These properties portray CXCR5+ T cells as a distinct memory T cell subset with B cell helper function, designated here as follicular B helper T cells (TFH).

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/3de52af7f9a91e1bc7f2d51b45dbd7a73b14d92f

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Citations in the corpus

Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production (2013, background): “It is specialized in providing help to B cells and is necessary for GC formation, Ig class switch, somatic hypermutation of antibody, and maturation of B cells into plasma cells and memory B cells (Breitfeld et al., 2000; Schaerli et al., 2000; Kim et al., 2001; Fazilleau et al., 2009a,b).”
The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. (2009, background): “, 1999), has enabled the identification of a specialized CD4 helpercell subset thatenters the folliclesduringT cell-dependent immune responses: follicular B helper T (Tfh) cells (Breitfeld et al., 2000; Kim et al., 2001; Schaerli et al., 2000).”
Role of CXCR5 and CCR7 in Follicular Th Cell Positioning and Appearance of a Programmed Cell Death Gene-1High Germinal Center-Associated Subpopulation1 (2007, background): “GC-associated T cells are typically enriched within the T zone distal pole of the GC, known as the light zone, and they express high levels of CXCR5 (8, 11, 12).”
Generation of follicular helper T cells is mediated by IL-21 but independent of TH1, TH2 or TH17 lineages (2008, background): “ICOS was previously shown to be expressed at high levels on human tonsillular CXCR5 T cells within the light zone of germinal centers and efficiently supported the immunoglobulin production (Breitfeld et al., 2000; Schaerli et al., 2000).”
Homing and cellular traffic in lymph nodes (2003, background): “Most T cells do not express CXCR5, but when CD4 + T cells encounter antigen they transiently upregulate the expression of this receptor and downregulate the expression of CCR7, which allows them to disengage from the T-cell area and migrate to the B-cell follicle”
T follicular helper (TFH) cells in normal and dysregulated immune responses. (2008, background): “Furthermore, CD4+ T cells from patients with XLP and from sap−/− mice are unable to upregulate ICOS expression in vivo and in vitro and are defective in production of B helper cytokines, such as IL-4 and IL-10 (70, 152, 156).”
CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. (2013, neutral): “Tfh cells are relative newcomers to the Th subset family (71, 72) and have not been previously described in nonhematological tumors.”
FOLLICULAR HELPER T CELLS: LINEAGE AND LOCATION (2009, background): “Tfh Cell Function In these earliest reports of Tfh cells, B helper cell function was assessed with CXCR5 Th cells from human tonsils (Breitfeld et al., 2000; Schaerli et al., 2000).”
Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion (2011, background): “Tfh cells express the chemokine (C-X-C motif) receptor 5 (CXCR5) 108 Immunity 34, 108–121, January 28, 2011 ª2011 Elsevier Inc. (Breitfeld et al., 2000; Kim et al., 2001; Schaerli et al., 2000), which allows their migration into B cell follicles in response to the specific ligand CXCL13.”