Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies

Transplantation. 1997 Nov 27;64(10):1432-7. doi: 10.1097/00007890-199711270-00010.


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).

Conclusion: Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.

MeSH terms

  • Adult
  • Antibodies / pharmacology*
  • Antilymphocyte Serum / pharmacology
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / physiology
  • Cyclosporine / pharmacology
  • Cytomegalovirus Infections / epidemiology
  • Female
  • Herpesviridae Infections / epidemiology
  • Herpesvirus 4, Human
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Incidence
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology
  • Longitudinal Studies
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology*
  • Male
  • Middle Aged
  • Muromonab-CD3 / pharmacology
  • Prednisolone / pharmacology
  • Prospective Studies
  • Regeneration
  • Time Factors
  • Tumor Virus Infections / epidemiology


  • Antibodies
  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Muromonab-CD3
  • Cyclosporine
  • Prednisolone