Removal of CD45+ cells from human fetal pancreas alters immunogenicity in vitro.
Human fetal pancreas (HFP) is a potential source of islets for the treatment of diabetes mellitus with the potential for growth and differentiation after transplantation. However, because of the small mass of a given HFP, multiple donors would be required for transplantation, thereby increasing the immunological challenge to the recipient. In this study, we investigate the contribution of hematopoietic cells to the immunogenicity of HFP. Single cell suspensions of HFP were depleted of CD45(+) cells using antibody-conjugated magnetic beads. In vitro mixed lymphocyte islet cultures were established using with CD45-depleted or nondepleted HFP. Depletion of CD45(+) cells resulted in the low levels of IFNgamma production at early time points (day 4), which increased to near normal levels by day 7. The development of donor-specific CTL was not consistently inhibited by CD45 cell depletion. The data suggests that CD45(+) cells within HFP are capable of stimulating immune responses by the direct pathway of antigen presentation, but that the indirect pathway is also involved in the development of CTL. The inhibition of early IFNgamma release, however, may be beneficial for the survival of transplanted islets. Therefore, the combination of CD45 depletion strategies with standard immunosuppressive drug therapies could result in better long-term survival of transplanted islets.
MacKenzie
D A
DA
University of Wisconsin, Department of Surgery, Madison, Wisconsin 53702, USA. macken@surgery.wisc.edu
Sollinger
H W
HW
Hullett
D A
DA
D000028:Abortion, Induced; D015703:Antigens, CD / Q000032:analysis; D005260:Female; D016332:Fetal Tissue Transplantation; D006801:Humans; D007515:Islets of Langerhans / Q000196:embryology / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008212:Lymphocyte Depletion / Q000379:methods; D009924:Organ Culture Techniques; D010179:Pancreas / Q000196:embryology* / Q000276:immunology; D011247:Pregnancy; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology; D014619:Vacuum Curettage / Q000379:methods
D015703:Antigens, CD; D017493:Leukocyte Common Antigens