Skin‐versus gut‐skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells

• Published in: European journal of immunology 2003-06, Vol.33 (6), p.1488-1496
• Main Authors: Iellem, Andrea, Colantonio, Lucia, D'Ambrosio, Daniele
• Format: Article
• Language: English
• Subjects: Adhesion molecule; Adult; Aging - immunology; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Blood - immunology; CD4 Antigens - analysis; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Adhesion; Cell trafficking; Chemokine CCL17; Chemokine CCL22; Chemokines, CC - pharmacology; Chemotaxis; Chemotaxis, Leukocyte - drug effects; Fetal Blood - cytology; Fetal Blood - immunology; Gene Expression Regulation; Humans; Immune Tolerance; Immunophenotyping; Infant, Newborn; Integrins - biosynthesis; Integrins - physiology; Intestines - immunology; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - physiology; Organ Specificity; Receptors, CCR4; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - drug effects; Receptors, Chemokine - genetics; Receptors, Chemokine - physiology; Receptors, Interleukin-2 - analysis; Receptors, Lymphocyte Homing - biosynthesis; Receptors, Lymphocyte Homing - genetics; Skin - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tolerance
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200323658

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 α4+β7+ 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 expressionof 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.