Porcine Fetal Ventral Mesencephalic Cells are Targets for Primed Xenoreactive Human T Cells

Cell Transplantation

Article

Jan Rozing¹  Michiel Staal²  Jan Koopmans²  Henk van Dijk³  Lou de Leij⁴  Elinda Bruin⁴  Aalzen De Haan⁴  Ieneke van der Gun⁴ 

[1] Department of Cell Biology, Section Immunology, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands;Department of Neurosurgery, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands;Department of Veterinary Anatomy and Physiology, University of Utrecht, Yalelaan 1, 3584 CL, The Netherlands;Medical Biology Section of Pathology and Laboratory Medicine, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands;

关键词: Xenotransplantation;    Ventral mesencephalon;    Parkinson's disease;    T cells;    Antibody-dependent cellular cytotoxicity (ADCC);    Porcine;   

DOI  :  10.3727/000000006783981846

 received in 2004-09-13, accepted in 2005-12-15,  发布年份 2006

来源: Sage Journals

【 摘 要 】

Xenotransplantation of porcine fetal ventral mesencephalic (pfVM) cells to overcome the dopamine shortage in the striatum of patients with Parkinson's disease seems a viable alternative to allotransplantion of human fetal donor tissue, especially because the latter is complicated by both practical and ethical issues. There is, however, little known about the xenospecific immune responses involved in such an intracerebral xenotransplantation. The aim of our study was to investigate whether 1) naive human peripheral blood mononuclear cells (PMBC) display cytotoxicity against pfVM cells of E28 pig fetuses, and 2) priming of human PBMC by xenogeneic antigen presenting cells (APC) modulates pfVM-directed cellular cytotoxicity. For this purpose fresh PMBC from nine individual donors were primed by incubation with either irradiated pfVM cells or porcine spleen cells (PSC) as APC in the presence of IL-2 for 1 week before assessing cytotoxicity in a 51Cr release assay. Also, direct NK reactivity and antibody-dependent cellular cytotoxicity (ADCC) of fresh PMBC against pfVM cells was assessed. No direct cytotoxicity of naive cells (either NK reactivity or ADCC) against pfVM cells could be determined. Only PMBC primed with PSC were capable of lysing pfVM cells. PBMC primed with pfVM cells did not show cytolytic capacity towards pfVM. Interestingly, large differences in xenospecific T-cell responses exist between individual donor PBMC. Thus, human T cells are capable of killing pfVM cells in a xenoreactive response, but only after priming by donor APC. The large interindividual differences between human donors in their xenoreactive response may influence patient selection for xenotransplantation and chances of graft survival for individual patients.

【 授权许可】

Unknown   
© 2006 Cognizant Comm. Corp.