PMID- 12694545 OWN - NLM STAT- MEDLINE DCOM- 20040408 LR - 20191107 IS - 0908-665X (Print) IS - 0908-665X (Linking) VI - 10 IP - 3 DP - 2003 May TI - Porcine CD80: cloning, characterization, and evidence for its role in direct human T-cell activation. PG - 252-8 AB - Previous studies has shown that human anti-pig reactivity in mixed lymphocyte cultures require the indirect presentation of antigens by human antigen presenting cells (APC). Xenoreactivity was inhibited by blockade of human costimulatory molecules. We investigated the role of porcine costimulatory molecules in their ability to activate human T cells directly. Porcine CD80 was cloned from lipopolysaccharide (LPS)-activated porcine lymphocytes. Sequence analysis showed a high degree of conservation in residues involved in CD28/CTLA4. COS cells transfected with porcine CD80 was able to activate human T cells in a cyclosporine independent manner, demonstrating that porcine CD80 can costimulate human T cells. Tumor necrosis factor-alpha (TNF-alpha) activated porcine splenocytes have been shown to up-regulate B7s. In order to test the effect of costimulation blockade in a xeno system, activated splenocytes were cultured with purified CD4+ T cells. The results demonstrated that these cells were capable of activating human T cells and this activation can be blocked by using an antihuman CD80 antibody that demonstrated cross-reactivity to porcine CD80. Non-cross reactive antibodies had no effect, again suggesting direct activation of the human T cells. These data suggest that a reagent that can block both the direct and indirect activation is necessary for a discordant xenotransplant. FAU - Tadaki, D K AU - Tadaki DK AD - NIDDK/Navy Transplantation and Autoimmunity Branch, Naval Medical Research Center, Bethesda, MD 20889-5600, USA. Tadakid@NMRC.Navy.mil FAU - Williams, A AU - Williams A FAU - Lee, K P AU - Lee KP FAU - Kirk, A D AU - Kirk AD FAU - Harlan, D M AU - Harlan DM LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Denmark TA - Xenotransplantation JT - Xenotransplantation JID - 9438793 RN - 0 (B7-1 Antigen) RN - 0 (Recombinant Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - B7-1 Antigen/chemistry/*genetics/*immunology MH - Base Sequence MH - Cloning, Molecular MH - Humans MH - Lymphocyte Activation/*immunology MH - Macaca mulatta MH - Models, Immunological MH - Molecular Sequence Data MH - Polymerase Chain Reaction MH - Protein Biosynthesis MH - Recombinant Proteins/immunology MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Swine MH - T-Lymphocytes/*immunology MH - Transfection MH - Transplantation, Heterologous EDAT- 2003/04/16 05:00 MHDA- 2004/04/09 05:00 CRDT- 2003/04/16 05:00 PHST- 2003/04/16 05:00 [pubmed] PHST- 2004/04/09 05:00 [medline] PHST- 2003/04/16 05:00 [entrez] AID - 2o004 [pii] AID - 10.1034/j.1399-3089.2003.02004.x [doi] PST - ppublish SO - Xenotransplantation. 2003 May;10(3):252-8. doi: 10.1034/j.1399-3089.2003.02004.x.