CXCR5⁺ CCR7⁻ CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

• Published in: European journal of immunology Vol. 37; no. 12; pp. 3352 - 3362
• Main Authors: Quigley, Máire F, Gonzalez, Veronica D, Granath, Anna, Andersson, Jan, Sandberg, Johan K
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01-12-2007; WILEY‐VCH Verlag
• Subjects: Adult; Antibody Formation; Antigens, CD - biosynthesis; Antigens, Differentiation, T-Lymphocyte - biosynthesis; B cells; B-Lymphocytes - cytology; B-Lymphocytes - immunology; CD8 Antigens - analysis; CD8 T cells; Cell Differentiation; Chemokine CXCL13 - pharmacology; Chemokines; Chemotaxis, Leukocyte - drug effects; Coculture Techniques; CXCR5; Cytokines - secretion; Germinal Center - cytology; Humans; Immunologic Memory - immunology; Inducible T-Cell Co-Stimulator Protein; Lymphocyte Activation; Lymphocyte Cooperation; Medicin och hälsovetenskap; Palatine Tonsil - cytology; Palatine Tonsil - immunology; Palatine Tonsil - ultrastructure; Receptors, CCR7 - analysis; Receptors, CXCR5 - analysis; Receptors, OX40 - biosynthesis; T cells; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200636746

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-γ 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.