IL-2 Pathway Blocking in Combination with Anti-CD154 Synergistically Establishes Mixed Macrochimerism with Limited Dose of Bone Marrow Cells and Prolongs Skin Graft Survival in Mice.
10.3346/jkms.2006.21.6.1005
- Author:
Jeong Hoon LEE
1
;
Jongwon HA
;
Shi Hwa KIM
;
Sang Joon KIM
Author Information
1. Department of Surgery, Hallym University College of Medicine, Chuncheon, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
ABI1793 monoclonal antibody;
Asnti-CD154;
abatacept;
CTLA4-Ig;
Anti-IL-2R;
Mixed Chimerism;
Transplantation Chimera;
Bone Marrow Transplantation;
Skin Transplantation;
Busulfan
- MeSH:
Skin Transplantation/*immunology/methods;
Mice, Inbred BALB C;
Mice;
Male;
Interleukin-2/*immunology;
Immunoconjugates/*administration & dosage;
Graft Survival/*immunology;
Drug Combinations;
CD40 Ligand/*immunology;
Bone Marrow Transplantation/*immunology/methods;
Antibodies/*administration & dosage/immunology;
Animals
- From:Journal of Korean Medical Science
2006;21(6):1005-1011
- CountryRepublic of Korea
- Language:English
-
Abstract:
To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5 x 10(7)) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of busulfan (25 mg/kg) on day-1. Recipients were grouped and injected the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to protocol. Mixed macrochimerism were induced in groups treated with anti-CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL-2R. Three groups having chimerism enjoyed prolonged graft survival more than 6 months. Superantigen deletion study revealed deletion of alloreactive T cells in combined blockade treated groups. In graft versus host disease model using CFSE staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154. However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154 can establish macrochimerism with limited dose of BM transplantation and induce specific tolerance to allograft.
