title: Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells.
abstract: In humans and rodents a population of naturally occurring CD4(+)CD25(+) T cells are suppressor T (CD25(+) Ts) cells, which are considered to maintain peripheral immunological tolerance. Recently, we have described a unique chemotactic response profile for human CD25(+) Ts cells, but their homing potential remains poorly defined. Here, we document a heterogeneous homing potential of human peripheral blood CD25(+) Ts cells consistent with their ability to mediate immunosuppression at distinct locations. Surprisingly, CD25(+)Ts cells are depleted of gut-homing integrin alpha(4) (+)beta(7) (+) T cells, while being enriched in skin-homing cutaneous lymphocyte antigen (CLA)(+) T cells. These findings document heterogeneous homing potential of peripheral blood-borne CD25(+) Ts cells with marked skewing for skin- versus gut-homing. Expression of CCR4 associates with both CD25 and CLA cell surface markers, being highest on CD4(+)CLA(+)CD25(+) T cells. Importantly, CD4(+)CD25(+) Ts cells isolated from human cord blood lack expression of CLA while expressing CCR4, suggesting intrinsic expression of CCR4 on CD25(+) Ts cells. These observations indicate that the increased expression of CCR4, which is proposed to guide CD25(+) Ts cells to DC, is an intrinsic feature of CD25(+) Ts cells.
authors.affiliation: BioXell, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Iellem
authors.forename: Lucia
authors.initials: L
authors.lastname: Colantonio
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Ambrosio
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D001769:Blood / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007231:Infant, Newborn; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D007422:Intestines / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D009928:Organ Specificity; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; D015704:CD4 Antigens; C063419:CTAGE1 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D016023:Integrins; D008562:Membrane Glycoproteins; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7