title: CXCR5+ CCR7- CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles.
abstract: Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5+ CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7low, and produced IFN-gamma and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5+ CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5+ CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population.
authors.affiliation: Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Máire F
authors.initials: MF
authors.lastname: Quigley
authors.forename: Veronica D
authors.initials: VD
authors.lastname: Gonzalez
authors.forename: Anna
authors.initials: A
authors.lastname: Granath
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
mesh_terms: D000328:Adult; D000917:Antibody Formation; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D054382:Chemokine CXCL13 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D018858:Germinal Center / Q000166:cytology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D054400:Receptors, CCR7 / Q000032:analysis; D054380:Receptors, CXCR5 / Q000032:analysis*; D053262:Receptors, OX40 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C515370:CCR7 protein, human; D016827:CD8 Antigens; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D016207:Cytokines; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human