title: Comparison of allogeneic and xenogeneic in vitro T-cell proliferative responses in sensitized patients awaiting kidney transplantation.
abstract: Highly sensitized patients awaiting kidney transplantation may be potential candidates for future clinical trials using pig organ donors. Because of crossreactivity between human leucocyte antigens (HLA) and swine leucocyte antigens (SLA), such patients might have heightened T-cell responses to porcine xenoantigens. We determined whether lymphocytes from allo-sensitized patients displayed secondary (cyclosporine resistant) T-cell proliferative responses against porcine xenoantigens. Lymphocytes from six non-sensitized, seven sensitized [immunoglobulin G (IgG) panel reactive antibodies (PRA) 11 to 84%], 14 highly sensitized patients (IgG PRA > 84%) and 12 healthy individuals were tested [in the presence and absence of Cyclosporin A (CsA)] to determine their proliferative response to human (allogeneic) and to porcine (xenogeneic) stimulator cells. Lymphocytes from all study groups showed a strong proliferative response to allogeneic and xenogeneic stimulator cells with no significant difference between non-sensitized and sensitized individuals. Addition of CsA (100 and 500 ng/ml) inhibited (>90%) proliferation of lymphocytes from all non-sensitized patients to both allogeneic and xenogeneic stimulators. CsA was less effective at inhibiting proliferation of lymphocytes from sensitized patients and highly sensitized patients to allogeneic stimulators [29% (n=21) and 50% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)]. In contrast, cyclosporine inhibited proliferation of lymphocytes from the majority of sensitized and highly sensitized patients to xenogeneic stimulator cells [14% (n=21) and 14% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)]. HLA sensitized patients awaiting renal transplantation display cyclosporine resistant proliferative T-cell responses to allogeneic stimulators but proliferative responses to xenogeneic stimulators are more amenable to suppression by CsA. This finding suggests that humoral sensitisation to HLA antigens is not necessarily indicative of a heightened in vitro T-cell response to SLA antigens.
authors.affiliation: Tissue Typing Laboratory, Addenbrooke's NHS Trust, Cambridge, UK.
authors.forename: Gertie J
authors.initials: GJ
authors.lastname: Oostingh
authors.forename: Hugh F S
authors.initials: HF
authors.lastname: Davies
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Taylor
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D016572:Cyclosporine / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015478:Antigens, Heterophile; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine