The effect of rabbit anti-thymocyte globulin induction therapy on regulatory T cells in kidney transplant patients

Nephrol Dial Transplant. 2009 May;24(5):1635-44. doi: 10.1093/ndt/gfn778. Epub 2009 Jan 28.


Background: Prevention of alloreactivity by rabbit anti-thymocyte globulins (rATG) may not only result from immunodepletion but also from the induction of T cells that control allogeneic immune responses. In the present prospective and controlled study, we investigated the effect of rATG on the frequency, function and phenotype of peripheral immunoregulatory CD4+ T cells in kidney transplant (KTx) patients.

Methods: After transplantation, 16 patients received ATG-induction therapy and triple therapy consisting of tacrolimus, MMF and steroids. The control group (n = 18) received triple therapy only. By flow cytometry, T cells were analysed for CD25, FoxP3, CD127, CD45RO and CCR7. To study their suppressive capacities, CD25bright T cells were co-cultured with CD25(-/dim) effector T cells (Teff) in mixed lymphocyte reactions (MLR), stimulated with donor and third party (3P) antigens.

Results: Pre-transplant levels of FoxP3+CD127(-/low) T cells were 6% of CD4+ T cells. One week post-ATG treatment, no measurable numbers of regulatory T cells were present (P < 0.01). After 4 weeks, the cell numbers of CD4+FoxP3+CD127(-/low) T cells slowly reappeared and thereafter remained low (P < 0.01). At 14 weeks, a significant shift towards the CD45RO+CCR7+ (central memory) phenotype within CD4+FoxP3+ T cells was observed (P < 0.01). At 26 weeks, the proliferative alloresponses of the PBMC and CD25(-/dim) Teff profoundly decreased compared to pre-transplant (P = 0.01 and P = 0.02 respectively), while the regulatory capacity of the CD25bright T cells, of which 90% consisted of FoxP3+CD127(-/low) T cells, remained unaffected. The CD25bright T cells suppressed the anti-donor (94%) and 3P responses (93%).

Conclusion: Our findings show that rATG therapy does not spare peripheral immunoregulatory T cells in vivo, but after regeneration preserves their suppressive activity.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antilymphocyte Serum / therapeutic use*
  • Cell Count
  • Coculture Techniques
  • Drug Therapy, Combination
  • Female
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Phenotype
  • Rabbits
  • Steroids / therapeutic use
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology*
  • Tacrolimus / therapeutic use


  • Antilymphocyte Serum
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Steroids
  • Mycophenolic Acid
  • Tacrolimus