title: Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7Ralphahigh cell population in solid organ transplant recipients.
abstract: It has been recently shown (Seddiki, N., B. Santner-Nanan, J. Martinson, J. Zaunders, S. Sasson, A. Landay, M. Solomon, W. Selby, S.I. Alexander, R. Nanan, et al. 2006. J. Exp. Med. 203:1693-1700.) that the expression of interleukin (IL) 7 receptor (R) alpha discriminates between two distinct CD4 T cell populations, both characterized by the expression of CD25, i.e. CD4 regulatory T (T reg) cells and activated CD4 T cells. T reg cells express low levels of IL-7Ralpha, whereas activated CD4 T cells are characterized by the expression of IL-7Ralpha(high). We have investigated the distribution of these two CD4 T cell populations in 36 subjects after liver and kidney transplantation and in 45 healthy subjects. According to a previous study (Demirkiran, A., A. Kok, J. Kwekkeboom, H.J. Metselaar, H.W. Tilanus, and L.J. van der Laan. 2005. Transplant. Proc. 37:1194-1196.), we observed that the T reg CD25(+)CD45RO(+)IL-7Ralpha(low) cell population was reduced in transplant recipients (P < 0.00001). Interestingly, the CD4(+)CD25(+)CD45RO(+)IL-7Ralpha(high) cell population was significantly increased in stable transplant recipients compared with healthy subjects (P < 0.00001), and the expansion of this cell population was even greater in patients with documented humoral chronic rejection compared with stable transplant recipients (P < 0.0001). The expanded CD4(+)CD25(+)CD45RO(+)IL-7Ralpha(high) cell population contained allospecific CD4 T cells and secreted effector cytokines such as tumor necrosis factor alpha and interferon gamma, thus potentially contributing to the mechanisms of chronic rejection. More importantly, CD4(+)IL-7Ralpha(+)and CD25(+)IL-7Ralpha(+) cells were part of the T cell population infiltrating the allograft of patients with a documented diagnosis of chronic humoral rejection. These results indicate that the CD4(+)CD25(+)IL-7Ralpha(+) cell population may represent a valuable, sensitive, and specific marker to monitor allospecific CD4 T cell responses both in blood and in tissues after organ transplantation.
authors.affiliation: Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Codarri
authors.forename: Laure
authors.initials: L
authors.lastname: Vallotton
authors.forename: Donatella
authors.initials: D
authors.lastname: Ciuffreda
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Venetz
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia
authors.forename: Karine
authors.initials: K
authors.lastname: Hadaya
authors.forename: Leo
authors.initials: L
authors.lastname: Buhler
authors.forename: Samuel
authors.initials: S
authors.lastname: Rotman
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D017493:Leukocyte Common Antigens