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  • Title: A CD4 domain 1 CC' loop peptide analogue enhances engraftment in a murine model of bone marrow transplantation with sublethal conditioning.
    Author: Varadi G, Friedman TM, Korngold R.
    Journal: Biol Blood Marrow Transplant; 2005 Dec; 11(12):979-87. PubMed ID: 16338620.
    Abstract:
    Host CD4(+) T cells that survive sublethal or even lethal preconditioning regimens can participate in the process of hematopoietic stem cell graft rejection, particularly when the transplantations are performed across a major histocompatibility complex (MHC) class II barrier. To enhance donor marrow engraftment, we tested the efficacy of a small synthetic cyclic heptapeptide, 802-2 (CNSNQIC), which was designed to closely mimic the CD4 domain 1 CC' surface loop, theoretically involved in CD4/MHC class II complex oligomerization and subsequent CD4(+) T-cell activation. Previously, this peptide was found to have inhibitory activity in murine models for CD4(+) T cell-dependent graft-versus-host disease and skin allograft rejection. Herein, we used the MHC class II--disparate bm12 --> B6-CD45.1 sublethal irradiation transplantation model to test the possibility that the 802-2 peptide could enhance the engraftment of donor T cell-depleted bone marrow (ATBM). Sublethally irradiated B6-CD45.1 mice that received bm12 ATBM in combination with the 802-2 peptide demonstrated increased donor marrow cell engraftment as compared with mice that received ATBM alone; this suggests that the 802-2 peptide may be useful as an immunomodulating agent to overcome MHC class II mismatch barriers in hematopoietic stem cell transplantation.
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