Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells.
The T helper (Th) cell pool is composed of specialized cells with heterogeneous effector functions. Apart from Th1 and 2 cells, CXCR5+ T cells have been suggested to be another type of effector T cell specialized for B cell help. We show here that CXCR5+ T cells are heterogeneous, and we identify subsets of CXCR5+ CD4 T cells that differ in function and microenvironmental localization in secondary lymphoid tissues. CD57+CXCR5 T cells, hereafter termed germinal center Th (GC-Th) cells, are localized only in GCs, lack CCR7, and are highly responsive to the follicular chemokine B lymphocyte chemoattractant but not to the T cell zone EBI1-ligand chemokine. Importantly, GC-Th cells are much more efficient than CD57-CXCR5+ T cells or CXCR5- T cells in inducing antibody production from B cells. Consistent with their function, GC-Th cells produce elevated levels of interleukin 10 upon stimulation which, with other cytokines and costimulatory molecules, may help confer their B cell helper activity. Our results demonstrate that CXCR5+ T cells are functionally heterogeneous and that the GC-Th cells, a small subset of CXCR5+ T cells, are the key helpers for B cell differentiation and antibody production in lymphoid tissues.
Kim
C H
CH
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. chkim@stanford.edu
Rott
L S
LS
Clark-Lewis
I
I
Campbell
D J
DJ
Wu
L
L
Butcher
E C
EC
D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001769:Blood / Q000276:immunology; D018959:CD57 Antigens / Q000032:analysis; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D008211:Lymphocyte Cooperation; D014066:Palatine Tonsil / Q000276:immunology; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
D015415:Biomarkers; C515460:CCL19 protein, human; D018959:CD57 Antigens; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054415:Chemokine CCL19; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D007136:Immunoglobulins; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine