title: ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells.
abstract: ICOS is expressed on activated T cells and particularly on CXCR5+ follicular Th cells in germinal centers (GC). Its deletion leads to a profound deficiency in memory B cell formation and switched Ab response in humans. Here, we show that in ICOS-deficient patients the generation of GCs is severely disturbed, and the numbers of circulating CXCR5+CD45RO+ memory CD4 T cells are significantly reduced, indicating an essential role of ICOS in the differentiation of CXCR5+CD4 T cells. The GC-specific CD57+CXCR5+ subpopulation is virtually absent. In ICOS-/- mice, the decrease of circulating CXCR5+CD4 T cells reflects the reduction of CXCR5+ follicular Th cells in lymph nodes and spleen. Therefore, in concurrence with the absence of CXCR5+ T cells in the blood of CD40L-deficient patients, these data support the hypothesis that circulating CD57+CXCR5+ T cells are GC derived and thus may serve as a surrogate marker for the presence of functional GCs in humans.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University Clinic Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bossaller
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Ruth
authors.initials: R
authors.lastname: Draeger
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.forename: Rolf
authors.initials: R
authors.lastname: Knoth
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Anne
authors.initials: A
authors.lastname: Durandy
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Michael
authors.initials: M
authors.lastname: Schlesier
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Welcher
authors.forename: Hans Hartmut
authors.initials: HH
authors.lastname: Peter
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine