Korean J Pediatr.  2004 Sep;47(9):919-925.

Regulatory T Cells and Allogeneic Transplantation

• Jeong DC

Abstract

Allogeneic organ or hematopoietic stem cell transplantation(HSCT) is the treatment of choice for end-stage organ diseases or various hematologic disorders. The induction of alloantigen specific T cell tolerance and its maintenance are critical for preventing immune responses, including graft rejection or graft-versus-host disease(GVHD) in allogeneic transplantation. CD4+ T cells are classified as immune functions : Th1 CD4+ cells for cellular immunity, Th2 for humoral immunity, Th3 for suppressive effect against activated T cells, Tr1 for regulation of immune response. Some CD4+ regulatory T cells have a major role in controlling immune response to alloantigen. A minor population of CD4+ T cells, which co-express the interleukin-2 receptor(IL-2R) alpha-chain(CD25), is crucial for the control of autoreactive T cells and for peripheral tolerance in allogeneic transplantation. CD4+CD25+ regulatory T cells express high level of cytotoxic T lymphocyte associated antigen 4(CTLA 4), as cell-contact mechanism, and secret immunomodulating cytokines, as IL-10 or TGF-beta, as independent cell contact. High expression of CTLA 4 on CD4+CD25+ T cells may contribute to deliver suppressive signals into T cells via CD28. Immature dendritic cells have low expression of major histocompatibility(MHC) and co-stimulatory signals, and few secretion of IL-12. CD4+CD25+ T cells are developed by immature myeloid dendritic cells, which are controlled under vitamin D3 or IL-10. In kidney transplantation, graft survival in recipients with donor specific transfusion(DST) showed longer than without DST. DST may induce antigen specific CD4+CD25+ T cells, and these cells play a role for central or peripheral tolerance against immune cells. In allogeneic HSCT, donor CD4+CD25+ T cells suppress lethal GVHD in MHC mismatched pairs, and also may possess graft-versus-leukemia effect in early infusion with HSC. We need more study for cytotoxic effect of CD4+CD25+ T cells, which have Fas-FasL interaction, although these cells in cancer patients suppress autoreactive T cells against tumor. Recently, many trials have investigated treatment for intractable disease using various types of cells, including mesenchymal stem cells, dendritic cells. We have to consider ex vivo expansion of CD4+CD25+ T cells for induction of immune tolerance in allogeneic transplantation. Now, we have to study or understand immunoregulatory cells for allogeneic transplantation or immune control.

Keyword

Allogeneic transplantation; CD4+CD25+ T cells