title: Decreased frequency of peripheral CD4(+) CD161(+)  Th(17) -precursor cells in kidney transplant recipients on long-term therapy with Belatacept.
abstract: Clinical trials have pointed out the promising role of co-stimulation blocker Belatacept for improvement of graft function and avoidance of undesired side-effects associated with calcineurin-inhibitors (CNI). However, due to the worldwide limited availability of appropriate patients, almost no data exist to assess the effects of sustained application of this immunomodulator on the recipient's immune system. The aim of this study was to reveal specific alterations in the composition of immunologic subpopulations potentially involved in development of tolerance or chronic graft rejection following long-term Belatacept therapy. For this, peripheral lymphocyte subsets of kidney recipients treated with Belatacept (n=5; average 7.8years) were determined by flow-cytometry and compared with cells from matched patients on CNI (n=9) and healthy controls (n=10). T cells capable of producing IL-17 and serum levels of soluble CD30 were quantified. Patients on CNI showed a higher frequency of CD4(+) CD161(+) Th(17) -precursors and IL-17-producing CD4(+) T cells than Belatacept patients and controls. Significantly higher serum levels of soluble CD30 were observed in CNI patients, indicating a possible involvement of the CD30/CD30L-system in Th(17) -differentiation. No differences were found concerning CD4(+) CD25(+) CD127(low) FoxP3(+) regulatory T cells. In conclusion, patients on therapy with Belatacept did not show a comparable Th(17) -profile to that seen in individuals with chronic intake of CNI. The distinct effects of Belatacept on Th(17) -immunity might prove beneficial for the long-term outcome following kidney transplantation.
authors.affiliation: Transplant Laboratory, Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany. vondran.florian@mh-hannover.de
authors.forename: Florian Wolfgang Rudolf
authors.initials: FW
authors.lastname: Vondran
authors.forename: Kai
authors.initials: K
authors.lastname: Timrott
authors.forename: Sonja
authors.initials: S
authors.lastname: Kollrich
authors.forename: Juergen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwinzer
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D065095:Calcineurin Inhibitors; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000032:analysis; D058504:Th17 Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D015704:CD4 Antigens; D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D020381:Interleukin-17; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D000069594:Abatacept