Human lymphocyte adhesion to xenogeneic porcine endothelial cells: modulation by human TNF-alpha and involvement of VLA-4 and LFA-1.
Considering that in the allogeneic situation the adhesion of recipient lymphocytes to donor endothelial cells initiates the cellular rejection, we questioned the possible occurrence of a similar process in the xenogeneic situation. The adhesion of human peripheral blood lymphocytes (PBL) to porcine aortic endothelial cells (PAEC) was thus studied in an in vitro porcine-to-human xenogeneic model. It was found that 25.9% of human PBL adhered to resting PAEC. Furthermore, this adhesion increased significantly when the PAEC were stimulated by the human cytokine TNF-alpha (tumor necrosis factor-alpha). The effect of human TNF-alpha was concentration- and time-dependent and was maximal (from 25.9% to 35.6%) with 100 U/ml during 6 h. Moreover, blocking experiments with monoclonal antibody (mAb) demonstrated the role of the PBL adhesion molecules LFA-1 and especially VLA-4. Indeed, an anti-CD11a mAb decreased PBL adhesion to resting PAEC by 17.1% and to TNF-alpha stimulated PAEC by 16.9%, whereas an anti-CD49d mAb decreased dramatically PBL adhesion to resting PAEC by 53.1% and to TNF-alpha stimulated PAEC by 41.0%. Finally, phenotypic analysis of the adherent PBL showed that 50.5% of adherent cells to resting PAEC were NK (natural killer) cells, whereas 50.7% of adherent cells to TNF-alpha stimulated PAEC were T lymphocytes, showing the preferential adhesion of NK cells to resting PAEC, and that the stimulation of the PAEC with human TNF-alpha affects predominantly T lymphocyte adhesion. These results indicate that human PBL could bind to xenogeneic PAEC and that this interaction could be a first step of a xenogeneic cellular rejection.
Birmele
B
B
Groupe Interactions Hôte-Greffon, Faculté de Médecine, Tours, France.
Thibault
G
G
Nivet
H
H
Gruel
Y
Y
Bardos
P
P
Lebranchu
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000502:physiology*; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature / Q000033:anatomy & histology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014183:Transplantation, Heterologous / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha