engleski

Mouse in vivo lymphohematopoietic recovery after transplantation of allogeneic bone marrow pretreated in vitro by cyclosporin A and dexamethasone

We have shown that the pretreatment of C57BL (H-2b) bone marrow cells with Cyclosporin A and Hydrocortisone (1 h at 37 C) alleviates graft-versus-host reaction (GVHR) that develops after the cells transplantation in lethally irradiated CBA (H-2k) mice. In the present study we investigated the underlying mechanisms of this effect, because the pretreatment could have not only alleviate the GVHR, but also enhance the hosts lymphohematopoietic recovery. C57BL bone marrow cells were first treated with anti-CD4 and anti-CD8 antibodies, or with control non-immune sera, then with 0,1 mg of both cyclosporin A and dexamethasone. The pharmacological pretreatment had no influence on survival of CBA mice which received T cell-depleated, but significantly enhanced the survival of recipients which received T cell non-depleated bone marrow. This revealed that the bone marrow T cells not only elicit the GVHR but also possibly enhance hosts lymphohematopoietic recovery. In another set of experiments, recipient mice were sacrificed every third day and lymphohematopoietic recovery was systematically analysed. The results suggested that the pharmacologic pretreatment of allogeneic bone marrow cells caused earlier appearance of spleen cell colonies (on 5th posttransplantation day), caused an early increase of concentration of peripheral blood leucocytes, and a late (20th posttransplantation day) increase of concentration of peripheral blood thrombocytes. These effects were also visible in syngeneic (CBA) donor-host combination. It appears that the pharmacological pretreatment of allogeneic bone marrow cells acts through bone marrow T lymphocytes, by suppressing their GVHR potential and enhancing their stimulation of lymphohematopoietic recovery.

GVHR; cyclosporin A; dexamethasone; mouse; bone marrow; T lymphocytes

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