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Regulatory function of human CD4+ cytolytic T lymphocytes
N J Poindexter1, M A Smith, A E Haynes
1Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Transplant Immunology
|June 22, 1999
Summary
CD4+ T cells may induce allograft tolerance by down-regulating CD8+ T cells. This study shows indirect CD4+ T cell recognition of donor peptides can lead to graft tolerance by suppressing CD8+ T cell activity.
Area of Science:
- Immunology
- Transplantation immunology
- T cell biology
Background:
- Allograft rejection involves CD4+ and CD8+ T cells.
- CD8+ T cells use cytolytic T lymphocyte (CTL) function via MHC class I recognition.
- CD4+ CTLs recognize MHC class II directly or indirectly via presented peptides.
Purpose of the Study:
- To investigate the role of CD4+ CTLs in allograft outcome.
- To test the hypothesis that indirect CD4+ CTLs down-regulate CD8+ CTLs.
- To explore a potential mechanism for achieving allograft tolerance.
Main Methods:
- Utilized an MHC class II-restricted CD4+ CTL line (MDSxA1/B8).
- Tested lysis of B lymphoblastoid cells pulsed with specific HLA-A1/B8 peptides.
- Assessed lysis of peptide-pulsed CD4+ and CD8+ T cell clones expressing HLA-DR4.
Main Results:
- MDSxA1/B8 cells lysed peptide-pulsed B lymphoblastoid cells.
- These CD4+ T cells also lysed peptide-pulsed CD4+ and CD8+ T cell clones expressing HLA-DR4.
- Lysis required processing and presentation of MHC class I peptides by the target T cell clones.
Conclusions:
- Indirectly recognizing CD4+ CTLs can down-regulate donor-specific CD8+ CTLs.
- Peptide-specific lysis by CD4+ CTLs may induce graft tolerance.
- This pathway offers a novel mechanism for achieving allograft tolerance.