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Related Experiment Videos

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

T F Müller1, S O Grebe, M C Neumann

  • 1Department of Nephrology, Philipps-University of Marburg, Germany.

Transplantation
|December 10, 1997
PubMed
Summary
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Long-term immunosuppression with antithymocyte globulin (ATG) in kidney transplant patients significantly alters T-cell subsets. ATG therapy causes dose-dependent, persistent decreases in CD4+ T-cells and increases in CD8+ T-cells for years post-transplant.

Area of Science:

  • Immunology
  • Transplantation Medicine
  • Cellular Biology

Background:

  • Clinicians understand the short-term immunosuppressive effects of antibody therapies.
  • Long-term immunological changes induced by these treatments remain largely unknown.
  • This study investigates the persistent effects of immunosuppressive antibodies in renal transplant recipients.

Purpose of the Study:

  • To evaluate the long-term impact of different immunosuppression protocols on T-cell subsets.
  • To compare the effects of basic immunosuppression, antithymocyte globulin (ATG), and OKT3 on lymphocyte populations post-renal transplantation.

Main Methods:

  • Prospective study of 43 renal allograft recipients categorized into Basic Immunosuppression (BI), Antithymocyte Globulin (ATG), and OKT3 groups.

Related Experiment Videos

  • Regular measurements of lymphocyte surface antigens (CD3, CD4, CD8, etc.), neopterin, serum amyloid A, and herpes virus status over a mean of 58.4 months.
  • Analysis focused on changes in T-cell subsets, particularly the CD4+/CD8+ ratio, and correlation with ATG dosage.

    • Main Results:

    • The Antithymocyte Globulin (ATG) group exhibited significantly and persistently lower CD4+/CD8+ T-cell ratios compared to BI and OKT3 groups.
    • Five years post-transplant, the ATG group showed a CD4+/CD8+ ratio of 0.6, versus 1.7 (OKT3) and 2.0 (BI).
    • This ratio inversion resulted from sustained CD4+ T-cell depletion and increased CD8+ T-cell regeneration, particularly CD8+brightCD57+ cells; CD4+ depletion correlated with cumulative ATG dose.

    Conclusions:

    • Polyclonal antibody therapy with Antithymocyte Globulin (ATG) induces dose-dependent, long-lasting alterations in T-cell subsets.
    • These immunological changes persist for years after renal transplantation.
    • The findings highlight the need for monitoring long-term immune reconstitution following ATG therapy.