title: Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes.
abstract: Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.
authors.affiliation: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Hartig
authors.forename: G W
authors.initials: GW
authors.lastname: Haller
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: S
authors.initials: S
authors.lastname: Kuhlenschmidt
authors.forename: P S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000328:Adult; D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013552:Swine / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015478:Antigens, Heterophile; D016207:Cytokines; D000939:Epitopes