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Human NK cell and ADCC reactivity against xenogeneic porcine target cells including fetal porcine islet cells
Author(s) -
KumagaiBraesch Makiko,
Satake Masahiro,
Qian Yunjian,
Holgersson Jan,
Möller Erna
Publication year - 1998
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.1998.tb00019.x
Subject(s) - antibody dependent cell mediated cytotoxicity , cytotoxic t cell , microbiology and biotechnology , antibody , lymphoblast , k562 cells , biology , peripheral blood mononuclear cell , immunology , interleukin 21 , immune system , cell culture , in vitro , chemistry , t cell , monoclonal antibody , leukemia , biochemistry , genetics
In vitro studies of human NK cell‐mediated cytotoxicity and ADCC against porcine target cells were performed. Stimulation of human PBMC responder cells with either allogeneic or xenogeneic porcine cells led to a marked increase in NK cell reactivity. Maximum reactivity was reached following 3–6 days of in vitro culture. The sensitivity of target cells ranked as follows: K562 > porcine PHA‐induced lymphoblasts > resting porcine PBMC. Limiting dilution analysis showed that allo‐ and xeno‐stimulation in vitro led to differentiation of similar frequencies of effector NK cells. Split culture experiments showed that single NK effector cells were cytotoxic against both K562 and porcine lymphoblasts, demonstrating that individual NK cells lack species specificity. NK effector cell generation stimulated by xenogeneic cells was cyclosporin A (CsA) sensitive and dependent on the presence of autologous responder T lymphocytes, a dependence that was completely reconstituted by the sole addition of human IL‐2. Xenostimulation of enriched CD3+ cells also led to a preferential appearance of CD 16+ or CD56+ lymphoblasts. Natural xenoreactive human anti‐porcine antibodies are mainly of IgM and IgG2 subclasses, but antibodies in xenoimmunised patients reactive against porcine lymphocytes and fetal porcine islet cells were also of IgG1 and IgG3 subclasses. The same subclass distribution was found among antibodies specific for galα1,3 gal epitopes as shown by tests performed with α1,3 galactosyltransferase‐transfected Raji cells (human Burkitt lymphoma cells). Natural antibodies did not mediate ADCC, whereas galα1,3 gal‐specific antibodies in sera from xenoimmunised patients did. Fetal porcine islet cells were sensitive to human NK cell‐mediated cytotoxicity and to ADCC mediated by xenoimmune sera.