title: Heterogeneity of CD4 and CD8+ memory T cells in localized and generalized Wegener's granulomatosis.
abstract: Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (positive for the long human isoform of CD45) phenotype. We analyzed patients with biopsy-proven localized Wegener's granulomatosis (WG) (n = 5), generalized WG (n = 16) and age- and sex-matched healthy controls (n = 13) to further characterize memory T cells in WG. The cell-surface expression of CD45RO, CD45RA, CD62L, CCR3, CCR5 and CXCR3 was determined on blood-derived T cells by four-color flow cytometric analysis. The fractions of CCR5+ and CCR3+ cells within the CD4+CD45RO+ and CD8+CD45RO+ memory T cell populations were significantly expanded in localized and generalized WG. The mean percentage of Th1-type CCR5 expression was higher in localized WG. Upregulated CCR5 and CCR3 expression could also be detected on a fraction of CD45RA+ T cells. CD62L expression was seen on approximately half of the memory T cell populations expressing chemokine receptors. This study demonstrates for the first time that expression of the inducible inflammatory chemokine receptors CCR5 and CCR3 on CD45RO+ memory T cells, as well as on CD45RA+ T cells ('revertants'), contributes to phenotypic heterogeneity in an autoimmune disease, namely WG. Upregulated CCR5 and CCR3 expression suggests that the cells belong to the effector memory T cell population. CCR5 and CCR3 expression on CD4+ and CD8+ memory T cells indicates a potential to respond to chemotactic gradients and might be important in T cell migration contributing to granuloma formation and vasculitis in WG.
authors.affiliation: Department of Rheumatology, University of Luebeck, and Rheumaklinik Bad Bramstedt, Ratzeburger Allee 160, 23538 Luebeck, Germany. lamprecht@rheuma-zentrum.de
authors.forename: Peter
authors.initials: P
authors.lastname: Lamprecht
authors.forename: Anika
authors.initials: A
authors.lastname: Erdmann
authors.forename: Antje
authors.initials: A
authors.lastname: Mueller
authors.forename: Elena
authors.initials: E
authors.lastname: Csernok
authors.forename: Eva
authors.initials: E
authors.lastname: Reinhold-Keller
authors.forename: Konstanze
authors.initials: K
authors.lastname: Holl-Ulrich
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
authors.forename: Hilke
authors.initials: H
authors.lastname: Bruehl
authors.forename: Wolfgang L
authors.initials: WL
authors.lastname: Gross
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*
chemical_list: C515350:CCR3 protein, human; C515187:CXCR3 protein, human; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D019041:L-Selectin; D017493:Leukocyte Common Antigens