PMID- 15561266 OWN - NLM STAT- MEDLINE DCOM- 20050505 LR - 20211203 IS - 0041-1345 (Print) IS - 0041-1345 (Linking) VI - 36 IP - 8 DP - 2004 Oct TI - CD8 T cell of donor splenocyte mixed with bone marrow cells is more effective than CD4 T cell for induction of donor-specific tolerance in sublethally irradiated mice. PG - 2418-22 AB - BACKGROUND: We previously demonstrated that even a low dose of bone marrow cells (BMCs) established donor-specific tolerance if mixed with splenocytes (SPLCs). In this study, T-cell subsets CD4 (CD4SP) and CD8 (CD8SP) of donor SPLCs were investigated for their contribution to the enhancement of BMC engraftment leading to donor-specific tolerance in sublethally irradiated mice. METHODS: Sublethally irradiated C57BL/6 recipient mice were intravenously injected BMCs mixing with CD4SP or CD8SP harvested from BALB/c donor mice. The degree of chimerism in the peripheral blood lymphocytes (PBLs) and in the SPLCs was analyzed using FACS, mixed lymphocyte reaction, and skin graft transplantation 3 months after injection. RESULTS: Recipients injected with 3 x 10(6) donor BMCs admixed with 10 x 10(6) donor CD8SP established chimerism. However, recipients injected with the same dose of BMCs admixed with 5 x 10(6) CD4SP, 10 x 10(6) CD4SP, and 5 x 10(6) CD8SP did not established chimerism. CD8SP contained 44% of Ly6A/E (Stem Cell Antigen-1 (Sca-1))-positive cells based on FACS analysis, whereas only 6% of CD4SP were positive for Ly6A/E. MLR supernates of donor SPLCs chimeric mice using admixture with CD8SP dominated by Th2 cytokines. In contrast, mixting with MLR supernates from failed chimera showed dominant Th1 cytokines. CONCLUSIONS: CD8SP seems to make a major contribution to enhance BMC engraftment and induce donor-specific tolerance. Ly6A/E (Sca-1)-positive cells need to be further investigated for their contribution to the establishment of chimerism. FAU - Yoshida, A AU - Yoshida A AD - Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan. FAU - Narumi, S AU - Narumi S FAU - Hashimoto, N AU - Hashimoto N FAU - Itabashi, Y AU - Itabashi Y FAU - Hakamada, K AU - Hakamada K FAU - Sasaki, M AU - Sasaki M LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Transplant Proc JT - Transplantation proceedings JID - 0243532 RN - 0 (Cytokines) SB - IM MH - Animals MH - Bone Marrow Transplantation/*immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cytokines/immunology MH - Female MH - Graft Survival/immunology MH - Immunosuppression Therapy/methods MH - Lymphocyte Culture Test, Mixed MH - *Lymphocyte Transfusion MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Models, Animal MH - Skin Transplantation/*immunology MH - Spleen/immunology MH - T-Lymphocyte Subsets/immunology MH - Whole-Body Irradiation EDAT- 2004/11/25 09:00 MHDA- 2005/05/06 09:00 CRDT- 2004/11/25 09:00 PHST- 2004/11/25 09:00 [pubmed] PHST- 2005/05/06 09:00 [medline] PHST- 2004/11/25 09:00 [entrez] AID - S0041-1345(04)00891-7 [pii] AID - 10.1016/j.transproceed.2004.08.028 [doi] PST - ppublish SO - Transplant Proc. 2004 Oct;36(8):2418-22. doi: 10.1016/j.transproceed.2004.08.028.