title: Kinetics of homeostatic proliferation and thymopoiesis after rATG induction therapy in kidney transplant patients.
abstract: BACKGROUND
  Lymphocyte-depleting therapy is associated with long-lasting effects on repopulated T cells and subsequent increased rates of infections and malignancies. The mechanisms of T-cell repopulation and their posttransplantation kinetics are not fully understood.
  
  
  METHODS
  We studied thymopoiesis by CD31(+) naïve T cells (recent thymic emigrants) and homeostatic proliferation by Ki-67(+) T cells in rabbit antithymocyte globulin (rATG)-treated patients the first 6 months after transplantation. Patients receiving basiliximab or no induction therapy served as controls.
  
  
  RESULTS
  At 6 months after transplantation, T-cell numbers were lower than before transplantation in rATG-treated patients, whereas T-cell numbers remained stable in both control groups. In this time period, thymopoiesis was similar between the three treatment groups; CD8(+) T cells showed the highest percentage of recent thymic emigrants. At month 1, percentages of Ki-67(+) naïve and memory CD4(+) and CD8(+) T cells were the highest in rATG-treated patients, but these percentages declined in the months thereafter. When CD31 was used to distinguish between cytokine- and antigen-driven proliferation in naïve T cells, we found evidence for cytokine-dependent proliferation. Cytokine-dependent proliferation was also shown by in vivo increased percentages of phosphorylated STAT5 and high expression levels of the interleukin-7 receptor-α and interleukin-15 receptor-α by T cells.
  
  
  CONCLUSIONS
  These findings demonstrate that, in the first month after rATG therapy, cytokine-induced homeostatic proliferation is involved in T-cell repopulation of both naïve and memory T cells. At later time points, the contribution of homeostatic proliferation diminished, which explains the observed incomplete T-cell recovery.
authors.affiliation: 1 Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 2 Address correspondence to: Anne P. Bouvy, M.D., Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Na-522, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Anne P
authors.initials: AP
authors.lastname: Bouvy
authors.forename: Marcia M L
authors.initials: MM
authors.lastname: Kho
authors.forename: Mariska
authors.initials: M
authors.lastname: Klepper
authors.forename: Nicolle H R
authors.initials: NH
authors.lastname: Litjens
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007155:Immunologic Factors