PMID- 8977310 OWN - NLM STAT- MEDLINE DCOM- 19970204 LR - 20171116 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 26 IP - 12 DP - 1996 Dec TI - Effect of CD80 and CD86 blockade and anti-interleukin-12 treatment on mouse acute graft-versus-host disease. PG - 3098-106 AB - We investigated the efficacy of a combination of anti-CD80 and CD86 (CD80 + 86) monoclonal antibodies (mAb), anti-interleukin (IL)-12 mAb, or both, for prophylaxis in a mouse acute graft-versus-host-disease (GVHD) model. The treatment with a combination of anti-CD80 + 86 mAb efficiently reduced the lethality of GVHD, whereas mAb against either CD80 or CD86 alone had an effect. A delay in lymphocyte reconstitution and GVHD-associated histological changes in organs was observed at 30 days post-bone marrow transplantation (BMT) even in the anti-CD80 + 86 mAb-treated mice, although these manifestations were resolved by 100 days. In vitro, host alloantigen-specific T cell proliferative responses and generation of CTL were significantly reduced by anti-CD80 + 86 treatment. Furthermore, anti-CD80 + 86 mAb preferentially inhibited the production of interferon (IFN)-gamma, but not IL-4 and IL-10, when cultures were assayed at 21 days. Although the anti-IL-12 mAb treatment alone inhibited the generation of cytotoxic T lymphocytes and IFN-gamma production in vitro, administration of anti-IL-12 mAb in vivo reversed the beneficial effects of anti-CD80 + 86 treatment on host survival post-BMT. The adverse effect of anti-IL-12 treatment seems to result from impairment of natural immunity and hematopoiesis, rather than as a consequence of an incomplete blockade of T helper (Th)1 responses. Our results suggest that the prevention of GVHD-induced death results from the efficient blockade of Th1 cell activation by the anti-CD80 + 86 treatment. However, further treatment is required for a complete prevention of GVHD, which seems to be partly mediated by Th2 cells. FAU - Saito, K AU - Saito K AD - Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan. FAU - Yagita, H AU - Yagita H FAU - Hashimoto, H AU - Hashimoto H FAU - Okumura, K AU - Okumura K FAU - Azuma, M AU - Azuma M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antibodies, Blocking) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (Cd86 protein, mouse) RN - 0 (Membrane Glycoproteins) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Acute Disease MH - Animals MH - Antibodies, Blocking/*pharmacology/therapeutic use MH - Antibodies, Monoclonal/*pharmacology/therapeutic use MH - Antigens, CD/*immunology MH - B7-1 Antigen/*immunology MH - B7-2 Antigen MH - Female MH - Graft vs Host Disease/mortality/*prevention & control/*therapy MH - Immunization, Passive MH - Interferon-gamma/antagonists & inhibitors/biosynthesis MH - Interleukin-10/antagonists & inhibitors/biosynthesis MH - Interleukin-12/biosynthesis/*immunology MH - Interleukin-4/antagonists & inhibitors/biosynthesis MH - Membrane Glycoproteins/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C3H MH - Mice, Inbred C57BL EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] AID - 10.1002/eji.1830261241 [doi] PST - ppublish SO - Eur J Immunol. 1996 Dec;26(12):3098-106. doi: 10.1002/eji.1830261241.