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T cell receptor beta-chain selection in human allograft rejection
1Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Journal of Immunology (Baltimore, Md. : 1950)
|January 1, 1989
Summary
T cells from kidney transplant rejection show specific DNA rearrangements. Analysis reveals both selection and expansion of T cell clones contribute to graft rejection.
Area of Science:
- Immunology
- Transplantation
- Molecular Biology
Background:
- Renal allograft recipients experiencing rejection exhibit T cell responses.
- T cell cytotoxicity against donor HLA and in vitro proliferation correlate with irreversible graft loss.
Purpose of the Study:
- To investigate T cell receptor (TCR) beta-chain gene rearrangements in T cell lines from rejected renal allografts.
- To determine the clonal origin of predominant TCR beta-chain rearrangements during kidney transplant rejection.
Main Methods:
- Establishment of T cell lines from renal needle biopsies of transplant recipients.
- Southern blot analysis using J beta C beta and J gamma DNA probes to detect TCR gene rearrangements.
- Analysis of sequential biopsies from a single patient to track clonal evolution.
Main Results:
- 10 out of 12 T cell lines displayed predominant TCR beta-chain rearrangements.
- Sequential biopsies from one patient showed consistent predominant beta-chain rearrangements over time.
- Analysis with a J gamma probe indicated that some predominant beta-chain rearrangements result from multiple T cell clones sharing similar rearrangements, while others suggest a single dominant clone.
Conclusions:
- Both selection of specific TCR beta-chain rearrangements and clonal expansion (dominance) occur during kidney transplant rejection.
- These processes lead to the observed predominant beta-chain rearrangements in T cells infiltrating rejected renal allografts.
- Understanding these clonal dynamics offers insights into the immunopathology of transplant rejection.