International Immunology, Vol. 13, No. 6, 747-755,
June 2001
© 2001 Japanese Society for Immunology
Renal transplant patients show variations in their self-reactive repertoires: a serial study
Heart Institute (InCor) and
1 Division of Renal Transplantation, Hospital of Clinics, University of São Paulo Medical School, Av. Dr Enéas de Carvalho Aguiar 500, 3a, São Paulo 05403-000, Brazil
2 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
3 Mental and Computational Biology, National Cancer Institute – Frederick, NIH, MD 21702-1201, USA
Correspondence to: V. Coelho
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.
Keywords: autologous limiting dilution assay, autoreactivity, multi-hit limiting dilution assay, regulatory cells, renal transplantation
Transmitting editor: G. J. Hämmerling
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