title: A possible role for specific "anergy" in immunologic hyporeactivity to donor stimulation in human kidney allograft recipients.
abstract: The low immunological reactivity toward donor cells usually observed in transplant recipients has been linked to clonal deletion or suppression of alloreactive cells. However, the anergy of donor-specific reactive cells is another possibility not extensively tested until now in humans. In this case, donor-specific reactive cells would be present and eventually be activated without becoming effector cells (i.e., without secreting IL-2 or becoming cytotoxic) after donor-specific stimulation. We studied 8 patients under low-dose immunosuppressive drugs who displayed hyporeactivity toward donor stimulation. IL-2 production, proliferative response, and cytotoxic activity toward donor cell stimulation was decreased (respectively 22, 53, and 19% of response toward third-party stimulation). In order to evidence anergy, we studied two activation markers (cell size increase and expression of IL-2 receptor [CD25]) in allografted recipient T cells after autologous (background), donor (experimental), and third-party cell stimulation (positive control). We showed that the percentage of CD25+ cells and the cell size increase were similar after donor or third-party cell stimulation and clearly above the background as early as days 1-2 after the beginning of the mixed lymphocyte culture. Moreover, CD4+ and CD8+ cells similarly expressed CD25 after donor or third-party stimulation. Thus, donor-specific reactive cells not only were present but could be activated without becoming effector cells. These data suggest that anergy may be an important phenomenon in allograft tolerance.
authors.affiliation: Cellular Immunology and Transplantation Laboratory, Institute for Scientific Research on Cancer, Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Alard
authors.forename: O
authors.initials: O
authors.lastname: Lantz
authors.forename: J Y
authors.initials: JY
authors.lastname: Perrot
authors.forename: G
authors.initials: G
authors.lastname: Chavanel
authors.forename: A
authors.initials: A
authors.lastname: Senik
authors.forename: B
authors.initials: B
authors.lastname: Charpentier
mesh_terms: D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2