Activated porcine embryonic brain endothelial cells induce a proliferative human T-lymphocyte response.
Transplantation of allogeneic embryonic neural tissue is a potential treatment for patients with Parkinson's and Huntington's diseases. The supply of human donor tissue is limited, and alternatives such as the use of animal (e.g., porcine) donor tissue are currently being evaluated. Before porcine grafts can be used clinically, strategies to prevent neural xenograft rejection must be developed. Knowledge on how human T lymphocytes recognize porcine embryonic neural tissue would facilitate the development of such strategies. To investigate the ability of porcine embryonic brain microvascular endothelial cells (PBMEC) to stimulate human T-cell proliferation, PBMEC were immuno-magnetically isolated and cocultured with purified human CD4 or CD8 single-positive T cells. PBMEC had a cobblestone-like growth pattern and expressed the endothelial cell markers CD31 and CD106. PBMEC stimulated with the supernatant of phytohemagglutinin-activated porcine peripheral blood mononuclear cells or porcine IFN-gamma, but not nonstimulated PBMEC, induced proliferation of both CD8 and CD4 T cells as assessed by [3H]thymidine incorporation. Flow cytometric analyses showed that the degree of CD8 and CD4 T cell proliferation correlated with the expression levels of class I and II major histocompatibility complex (MHC) antigens, respectively. PBMEC expressed a CTLA-4/Fc-reactive molecule, most likely CD86, suggesting that these cells are able to deliver a costimulatory signal to the T cells. Human TNF-alpha, but not human IFN-gamma, induced class I, but not class II, MHC expression on PBMEC. Within a neural graft or the regional lymph nodes, PBMEC might stimulate human T cells via the direct pathway, and should therefore be removed from the donor tissue prior to transplantation.
Division of Clinical Immunology, Karolinska Institutet, Huddinge University Hospital AB, S-141 86 Stockholm, Sweden.
Suchitra
S
Sumitran-Holgersson
Thomas
T
Brevig
Håkan
H
Widner
Jan
J
Holgersson
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D016380:Brain Tissue Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D042783:Endothelial Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D005333:Fetus; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D019636:Neurodegenerative Diseases / Q000628:therapy; D034421:Sus scrofa; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000276:immunology* / Q000379:methods
D000954:Antigens, Surface; D016207:Cytokines