title: Xenogeneic cells and superantigen induce human T-cell activation in the absence of T-cell recognition of xenoantigen.
abstract: The extent of interaction between human T-lymphocytes and xenogeneic antigen-presenting cells (APCs) is species-dependent. A successful interaction requires high-affinity receptor-ligand pairing across species and recognition of antigens presented by foreign major histocompatibility complex (MHC). A deficient human T-lymphocyte response to xenogeneic cells is likely the result of a defect in these interactions. However, the requirements for a T-cell response to superantigen (SAg) may differ from those of other T-cell responses. Using irradiated murine splenocytes, which are believed to be incapable of eliciting human T-cell responses, and porcine aortic endothelial cells (PAECs) as the APC populations, we studied the human T-lymphocyte response to antigens presented by these cells. Direct proliferation of human T-lymphocytes to SAg presented by murine APCs was demonstrated; it was blocked by anti-human LFA-1 and anti-murine MHC class II but not by anti-human MHC class II. PAECs also presented SAg to human T-cells, generating a proliferative response greater than the primary response to porcine xenoantigen. Culture of human T-cells with murine splenocytes or PAECs and SAg Staphylococcus enterotoxin A (SEA) for 7 days primed human T-cells to proliferate in a secondary culture in response to autologous APCs. This autologous secondary response was human MHC class II-dependent and was inhibited by anti-human LFA-1, anti-human CD2, and anti-human CD98. Surprisingly, both of these responses were also blocked by anti-SEA, suggesting that despite vigorous washing, a small amount of functionally important SAg was carried over from primary to secondary culture, probably bound to the surface of T-cells. Xenogeneic APCs, even those that fail to stimulate human T-cells directly, can serve as APCs for primary human T-cell responses. After such interactions T-cells can develop secondary responses in autologous interactions based on retention of minute amounts of SAg. Such interactions may have important implications for xenotransplantation.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, 48109, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Rajiv
authors.initials: R
authors.lastname: Pai
authors.forename: Judith
authors.initials: J
authors.lastname: Endres
authors.forename: Paul
authors.initials: P
authors.lastname: Anthony
authors.forename: Christina
authors.initials: C
authors.lastname: Duzyj
authors.forename: Shree
authors.initials: S
authors.lastname: Bishu
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Morita
authors.forename: David A
authors.initials: DA
authors.lastname: Fox
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D001011:Aorta / Q000166:cytology; D018801:CD2 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology; D027261:Fusion Regulatory Protein-1 / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D018089:Superantigens / Q000276:immunology*; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D015478:Antigens, Heterophile; D018801:CD2 Antigens; D004768:Enterotoxins; D027261:Fusion Regulatory Protein-1; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal