Human T-cell-porcine endothelial cell interactions induce human Th1 cytokines and porcine activation markers.

Since the future of clinical transplantation will undoubtedly include xenotransplantation, there is a need to examine human anti-pig cellular reactions. The objective of this study is to use human anti-porcine mixed lymphocyte endothelial cell culture (MLEC) to investigate cell interactions, cross-species molecular compatibilities, and the induction of human cytokines and porcine activation markers. Human peripheral blood mononuclear cells or enriched CD4+ T cells depleted of professional antigen-presenting cells were cultured with resting pig aortic endothelial cells in the absence of exogenous cytokines. T-cell proliferative responses were measured and PAEC were monitored for cell surface markers by flow cytometry. Culture supernatants were assayed for human TNF-alpha and IFN-gamma by ELISA. Human T cells proliferated strongly in response to PAEC (median stimulation index = 75), even in serum-free cultures. High levels of the human Th1 cytokines TNF-alpha (20-350 pg/ml) and IFN-gamma (200-3800 pg/ml) were detected only in cultures containing PAEC, with levels peaking on Day 4. CD4+ T-cell-enriched, APC-depleted responders maintained proliferative anti-PAEC responses and cytokine release. By Day 3, MHC Class II and VCAM expression was induced in 92-96% PAEC: mean fluorescence intensity (MFI) increased from 5 to 83 +/- 12 and 166 +/- 74, respectively, and MHC Class I was increased from MFI 31 to 965 +/- 269. These results indicate that MLEC is an excellent in vitro model in which to study human anti-porcine cellular responses. Human T cells are activated in response to direct antigen presentation by PAEC, which are also activated in this system. Specific cytokines, receptors, and adhesion molecules appear to cross the xenograft barrier and play a critical role in T-cell - PAEC interactions. Such interactions are likely to affect VEC activation and immune responses to porcine xenografts in vivo.

Coleman TS ，Pittman HK ，Purser SM ，Haisch CE ，Verbanac KM ... -  《JOURNAL OF SURGICAL RESEARCH》

Effect of human cytokines (IFN-gamma, TNF-alpha, IL-1 beta, IL-4) on porcine endothelial cells: induction of MHC and adhesion molecules and functional significance of these changes.

Batten P ，Yacoub MH ，Rose ML 《-》

Evidence that activation of human T cells by porcine endothelium involves direct recognition of porcine SLA and costimulation by porcine ligands for LFA-1 and CD2.

Rollins SA ，Kennedy SP ，Chodera AJ ，Elliott EA ，Zavoico GB ，Matis LA ... -  《TRANSPLANTATION》

Human T lymphocyte proliferative response to resting porcine endothelial cells results from an HLA-restricted, IL-10-sensitive, indirect presentation pathway but also depends on endothelial-specific costimulatory factors.

Vallée I ，Guillaumin JM ，Thibault G ，Gruel Y ，Lebranchu Y ，Bardos P ，Watier H ... -  《JOURNAL OF IMMUNOLOGY》

Evidence of noninvolvement of swine MHC class II in the in vitro proliferative response of human lymphocytes to porcine endothelial cells.

Vallée I ，Watier H ，Thibault G ，Salmon H ，Gruel Y ，Lebranchu Y ，Bardos P ... -  《TRANSPLANTATION》