title: Altered balance between effector T cells and FOXP3+ HELIOS+ regulatory T cells after thymoglobulin induction in kidney transplant recipients.
abstract: This study examined the effect of thymoglobulin induction therapy on leukocyte population dynamics in kidney transplant patients. Patients receiving standard immunosuppression were compared with those who received additional thymoglobulin at the time of kidney transplantation. Thymoglobulin induction led to an immediate and significant decrease of all T cells and NK cells, but not B cells or monocytes. CD8(+)  T cells recovered to near pretransplant level by 4 weeks post-transplant. CD4(+)  T cells remained at less than 30% of pretransplant level for the entire study period of 78 weeks. Both CD4(+)  and CD8(+)  T cells showed reduced cytokine production after recovery. Deletion of CD4(+) FOXP3(+) HELIOS(+)  regulatory T cells (Tregs) was less profound than that of CD4(+) FOXP3(-)  cells, thus the relative percentage of Tregs elevated significantly when compared with pretransplant levels in thymoglobulin-treated patients. In contrast, the percentages of Tregs and their expression of FOXP3 in the standard immunosuppression group decreased steadily and by 12 weeks after transplant the average percentage of Tregs was 56% of the pretransplant level. Thus, thymoglobulin-induced deletion of T cells led to significant and long-lasting alterations of the T-cell compartment characterized by a preservation of Tregs and long-lasting reduction in CD4(+) , and potentially pathogenic, T cells.
authors.affiliation: Department of Surgery, University of California-San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA. qizhi.tang@ucsfmedctr.org
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Tang
authors.forename: Joey
authors.initials: J
authors.lastname: Leung
authors.forename: Kristin
authors.initials: K
authors.lastname: Melli
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lay
authors.forename: Emmeline L
authors.initials: EL
authors.lastname: Chuu
authors.forename: Weihong
authors.initials: W
authors.lastname: Liu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Sang-Mo
authors.initials: SM
authors.lastname: Kang
authors.forename: V Ram
authors.initials: VR
authors.lastname: Peddi
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000961:Antilymphocyte Serum; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C512542:thymoglobulin