A CD4 domain 1 CC' loop peptide analogue enhances engraftment in a murine model of bone marrow transplantation with sublethal conditioning.
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.
Varadi
Gabor
G
Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Friedman
Thea M
TM
Korngold
Robert
R
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D015704:CD4 Antigens / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D018448:Models, Immunological; D009842:Oligopeptides / Q000008:administration & dosage* / Q000276:immunology; D017434:Protein Structure, Tertiary; D019172:Transplantation Conditioning / Q000379:methods
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides