Renal transplant patients show variations in their self-reactive repertoires: a serial study

Int Immunol. 2001 Jun;13(6):747-55. doi: 10.1093/intimm/13.6.747.

Abstract

We addressed the question of whether allo-transplantation (Tx) induces breakdown of tolerance to self-antigens or alteration of the autoreactive T cell repertoire in humans. The serial variation of T cell autoreactivity was studied in the peripheral blood of 12 renal transplant patients, by autologous limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood mononuclear cells in the post-Tx period, in contrast to four of 12 patients before Tx (P = 0.038). Multi-hit kinetics was found in 57% of the assays analyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in precursor frequency at >1 year post-Tx in five patients. These data indicate that autoreactivity increases or develops following Tx, in humans. Post-Tx events such as alloreactivity, infections or immunosuppression could interfere with the balance of autoreactive and regulatory cells, leading to changes in the T cell repertoires to self-antigens and eventually breakdown of self-tolerance. Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over alloreactivity or both, at separate times.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantigens / immunology
  • Blood Transfusion
  • Child, Preschool
  • Clone Cells
  • Female
  • Humans
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / methods
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphocyte Culture Test, Mixed
  • Male
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • Self Tolerance / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transplantation Tolerance / immunology
  • Transplantation, Homologous

Substances

  • Autoantigens
  • Phytohemagglutinins