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Arch Hellen Med, 27(3), May-June 2010, 529-538


Immune tolerance induced by the inhibition of CD18 alone or both signal transducer
and activator of transcription 3 (Stat3) and islet/duodenum homeobox-1 (IDX-1)
at the time of rat bone marrow (BM) transplantation in which thymus T lymphopoiesis occurred post-transplantation

Department of Transfusion Cell Therapy, Hamamatsu University School of Medicine, Hamamatsu, Japan

OBJECTIVE To elucidate the mechanism of immune tolerance and demonstrate its occurrence clinically and in vitro.

METHOD Rat bone marrow (BM) trans-plantation was performed using F1 (DAxLEW) hybrid hosts and DA donors, which were followed for 127-157 days post-transplantation. BM cells were injected together with both signal transducer and activator of transcription 3 (Stat3) and islet/duodenum homeobox-1 (IDX-1) antibodies (Abs) or CD18 Ab alone into the host spleen onto which a piece of donor spleen was trans-planted.

RESULTS When DA BM cells were injected with Stat3 and IDX-1 Abs or CD18 Ab, chronic graft versus host disease (GvHD) symptoms, such as body weight loss, thymus atrophy, intestinal disturbances and alopecia, were not displayed. The F1 females without clinical GvHD showed increased numbers of megakaryocytes in their BM, no extramedullary hematopoiesis, and flow cytometer (FCM) activation of Stat3 in the BM and thymus, and CD11b, CD18 and IDX-1 in the host and graft spleens. The correlation coefficient between the Stat3+ thymus cells and DIX-1+ spleen cells of the females without GvHD signs was 0.58, while that of the control females was 0.4. Immuno-chemical electron micrographs showed mitochondrial IDX-1 proteins specifically, as well as Stat3 in the females with immune tolerance.

CONCLUSIONS Immune tolerance was induced by the inhibition of Stat3 and IDX-1, which has a nega-tive interaction with Stat3, at the time of BM transplantation. Post-transplant CD18 rebound stimulated thymus T cell proliferation. Spleen production of insulin-like growth factor 1 (IGF-1) must promote immune tolerance without clinical GvHD symptoms.

Key words: Bone marrow transplantation, CD18, Chronic graft versus host disease, Immune tolerance, Spleen graft, Thymus.

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