title: Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies.
abstract: BACKGROUND
  Clinicians are well aware of the short-term effects of immunosuppression by mono- or polyclonal antibodies. Little is known about long-term changes induced by these therapies.
  
  
  METHODS
  Forty-three renal allograft recipients were selected according to their initial postoperative immunosuppression: (1) BI group=basic immunosuppression with steroids and cyclosporine, n=16; (2) ATG group=basic immunosuppression plus polyclonal antibody antithymocyte globulin (ATG), n=11; and (3) OKT3 group=basic immunosuppression plus monoclonal antibody OKT3, n=16 patients. At intervals of 6 months, the following parameters were measured prospectively: lymphocyte surface antigens (HLA-DR, CD3, CD4, CD8, CD16, CD19, CD56, and CD57); serum and urine neopterin; serum amyloid A; and indirect and direct tests for herpes viruses.
  
  
  RESULTS
  The mean period of observation was 58.4 months. The most significant differences between the groups occurred for CD4+ and CD8+ T cells. The ratios of CD4+ to CD8+ cells (n=278 measurements) were significantly and persistently lower in the ATG group (P<0.001, Brown-Mood test). Five years after transplantation, the ATG group had a CD4+ to CD8+ cell ratio of x=0.6 versus x=1.7 in the OKT3 group and x=2.0 in the BI group. This inversion was due to a persistent depletion of the CD4+ cells and an increased regeneration of the CD8+ cells, in particular of the CD8+brightCD57+ subpopulation. Extent and duration of CD4+ depletion correlated with the cumulative ATG dose (r=0.7, P<0.05, Spearman rank correlation test).
  
  
  CONCLUSIONS
  Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.
authors.affiliation: Department of Nephrology, Philipps-University of Marburg, Germany.
authors.forename: T F
authors.initials: TF
authors.lastname: Müller
authors.forename: S O
authors.initials: SO
authors.lastname: Grebe
authors.forename: M C
authors.initials: MC
authors.lastname: Neumann
authors.forename: J
authors.initials: J
authors.lastname: Heymanns
authors.forename: K
authors.initials: K
authors.lastname: Radsak
authors.forename: H
authors.initials: H
authors.lastname: Sprenger
authors.forename: H
authors.initials: H
authors.lastname: Lange
mesh_terms: D000328:Adult; D000906:Antibodies / Q000494:pharmacology*; D000961:Antilymphocyte Serum / Q000494:pharmacology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D003586:Cytomegalovirus Infections / Q000453:epidemiology; D005260:Female; D006566:Herpesviridae Infections / Q000453:epidemiology; D004854:Herpesvirus 4, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology; D008137:Longitudinal Studies; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D011446:Prospective Studies; D012038:Regeneration; D013997:Time Factors; D014412:Tumor Virus Infections / Q000453:epidemiology
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D011239:Prednisolone