title: Persistence of Indirect but Not Direct T Cell Xenoresponses in Baboon Recipients of Pig Cell and Organ Transplants.
abstract: We investigated the contributions of direct and indirect T cell antigen recognition pathways to the immune response to porcine antigens in naïve baboons and baboon recipients of pig xenografts. In naïve baboons, in vitro culture of peripheral blood T cells with intact pig cells (direct xenorecognition pathway) or pig cell sonicates and baboon antigen-presenting cells (indirect xenorecognition pathway) induced the activation and expansion of xenoreactive T cells producing proinflammatory cytokines, interleukin-2 and interferon-γ. Primary indirect xenoresponses were mediated by preexisting memory T cells, whose presence is not typically observed in primary alloresponses. Next, baboons were conditioned with a nonmyeloablative regimen before short-term immunosuppression and transplantation of xenogeneic peripheral blood progenitor cells and a kidney, heart, or pancreatic islets from a miniature swine. All transplants were rejected acutely within 30 days after their placement. Posttransplantation, we observed an inhibition of the direct xenoresponse but a significant expansion of indirectly activated proinflammatory T cells. These results suggest that additional treatment to suppress indirect T cell immunity in primates may be required to achieve tolerance of pig xenografts through hematopoietic chimerism.
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: L
authors.initials: L
authors.lastname: Buhler
authors.affiliation: Transplantation Unit, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: B M-W
authors.initials: BM
authors.lastname: Illigens
authors.affiliation: Transplantation Unit, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: O
authors.initials: O
authors.lastname: Nadazdin
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Tena
authors.affiliation: Transplantation Unit, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: D K C
authors.initials: DK
authors.lastname: Cooper
authors.affiliation: Transplantation Unit, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: G
authors.initials: G
authors.lastname: Benichou
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D064593:Heterografts; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016377:Organ Transplantation; D010215:Papio; D036102:Peripheral Blood Stem Cell Transplantation; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma