EFFECT OF FK506 AND ANTI-CD4 THERAPY ON FETAL PIG PANCREAS XENOGRAFTS AND HOST LYMPHOID-CELLS IN NOD/LT, CBA, AND BALB/C MICE
- Author(s)
- AKITA, K; Ogawa, M; Mandel, TE;
- Details
- Publication Year 1994-01,Volume 3,Issue #1,Page 61-73
- Journal Title
- CELL TRANSPLANTATION
- Publication Type
- Journal Article
- Abstract
- Varying doses of FK506, and a cell-depleting anti-CD4 monoclonal antibody, GK1.5, were tested as either monotherapy or in combination for their effect on the survival of renal subcapsular xenografts of organ-cultured fetal pig pancreas in three strains of mice. Subcutaneous injections of FK506 at 4.0 mg/kg/day for 28 d prevented graft rejection to day 35 posttransplantation (i.e., 7 days after cessation of treatment in NOD/Lt, and CBA mice) while BALB/c mice had intact grafts at 28 days. Lower doses were less effective and immunosuppression was less effective in NOD mice than in the other strains. Even 2.0 mg/kg/day of FK506 prevented rejection in CBA mice until day 35, but not in NOD/Lt mice. GK1.5 alone did not prevent rejection in NOD/Lt mice but when a low dose of FK506 (2.0 mg/day) was added, the grafts were present, essentially intact, at 35 days. There were no obvious toxic effects of FK506 in NOD/Lt and CBA mice. With FK506 treatment there was no significant difference in absolute numbers of total leucocytes or lymphocytes in peripheral blood and spleen, but there was a decrease in thymus cellularity. Flow cytometric analysis of lymphocyte subsets in blood and spleen also showed no significant differences, but in the thymus the percentage of immature CD4/CD8 ''double positive'' cells increased while the more mature CD3 ''high'', and CD4 or CD8 ''single-positive'' cells decreased. Thus, prolonged discordant xenograft survival in mice is possible and the use of two agents that act on different parts of the immune system allows a reduction in the dose of FK506 to safe levels.
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- CYCLOSPORINE-A; IMMUNOSUPPRESSIVE AGENT; PROISLET XENOGRAFTS; GLUCOSE-METABOLISM; DIABETIC MICE; FK-506; RATS; ACTIVATION; SURVIVAL; ISLETS
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Creation Date: 1994-01-01 12:00:00