CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function.
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 (T(FH)).
Schaerli
P
P
Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland. patrick.schaerli@tki.unibe.ch
Willimann
K
K
Lang
A B
AB
Lipp
M
M
Loetscher
P
P
Moser
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000502:physiology; D019743:Chemokines, CXC / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016201:Receptors, Lymphocyte Homing; D017493:Leukocyte Common Antigens