title: Association of high IFN-gamma plasma levels with low B-cell counts in renal transplant recipients with stable long-term graft function.
abstract: Recently, we reported that patients with long-term stable good graft function had higher interferon-gamma (IFN-gamma) and lower IL-4 plasma levels late as compared with early post-transplant. These patients had more often detectable CD3(+)CD4(+)CD25(+)IFN-gamma(+)Foxp3(+) peripheral blood lymphocytes (PBL) late post-transplant than patients with impaired graft function. We therefore speculated that high plasma IFN-gamma late post-transplant might contribute to the maintenance of graft acceptance. Using ELISA and four-color flow cytometry, plasma cytokines and PBL subpopulations were measured in 65 renal transplant recipients with stable graft function late post-transplant. High IFN-gamma plasma levels were associated with low CD19(+) B PBL (r = -0.329; p = 0.009) and low activated CD3(+)CD8(+)DR(+) T PBL (r = -0.266; p = 0.035). Plasma IFN-gamma increased with time post-transplant (r = 0.288; p = 0.022) and was not associated with the dose of immunosuppressive drugs (p = n.s.). High plasma IFN-gamma was not associated with serum creatinine (r = 0.038; p = 0.765). Five patients showed evidence of chronic allograft nephropathy in previous biopsies and none of them exhibited increased plasma IFN-gamma. In patients with good long-term graft function, high IFN-gamma plasma levels were associated with low numbers of B PBL and activated CD8(+) T PBL. High IFN-gamma plasma levels might prevent the development of an immunological alloresponse and thereby contribute to the maintenance of graft acceptance.
authors.affiliation: Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany. volker.daniel@med.uni-heidelberg.de
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.forename: Cord
authors.initials: C
authors.lastname: Naujokat
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Fabrice Christoph
authors.initials: FC
authors.lastname: Renner
authors.forename: Rolf
authors.initials: R
authors.lastname: Weimer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D016207:Cytokines / Q000097:blood; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D055815:Young Adult
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D015847:Interleukin-4; D007371:Interferon-gamma