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Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes
Author(s) -
Tahara Hiroyuki,
Ide Kentaro,
Basnet Nabin,
Tanaka Yuka,
Ohdan Hideki
Publication year - 2010
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.1399-3089.2010.00575.x
Subject(s) - peripheral blood mononuclear cell , xenotransplantation , mixed lymphocyte reaction , microbiology and biotechnology , transplantation , cd8 , t cell , immunology , chemistry , andrology , biology , immune system , medicine , in vitro , biochemistry
Tahara H, Ide K, Basnet N, Tanaka Y, Ohdan H. Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes. Xenotransplantation 2010; 17: 188–196. © 2010 John Wiley & Sons A/S. Abstract: Background: It is acknowledged that the response of human T cells to xenogeneic targets is more potent than that to allogeneic targets. However, it is not clear whether the more vigorous T cell response to xenoantigens than to alloantigens is attributable to a higher frequency or stronger reaction of xenoreactive T cells. Methods: We determined the precursor frequencies (PFs) and stimulation indexes (SIs) of xenoreactive human T cells by performing a mixed lymphocyte reaction (MLR) assay using a carboxyfluorescein diacetate succinimidyl ester (CFSE)‐labeling technique. Irradiated porcine or human peripheral blood mononuclear cells (PBMCs)used as stimulator cells—were cultured with CFSE‐labeled human PBMCs—used as responder cells. Results: The SIs of the xenoreactive CD4 + T cells were significantly higher than those of the alloreactive CD4 + T cells, whereas the PFs of the alloreactive and xenoreactive CD4 + T cell precursors were almost identical, suggesting a stronger reaction by a single xenoreactive CD4 + T cell. In contrast, the SIs of the xenoreactive CD8 + T cells did not differ from those of the alloreactive CD4 + T cells, and the PFs of the allo‐ and xenoreactive CD8 + T cell precursors were also identical. Addition of a soluble human CD47‐Fc fusion protein in the porcine‐to‐human MLR assay caused a statistically significant reduction of the SIs of the xenoreactive CD4 + T cells. Such an alteration was abrogated by further addition of blocking antibodies (Abs) against either human CD47 or signal regulatory protein‐α in the porcine‐to‐human MLR assay. Addition of human CD47‐Fc after the depletion of non‐T cells from the population of human responder PBMCs in this MLR assay did not influence the SIs of the xenoreactive CD4 + T cells. Conclusions: The more vigorous T cell response to xenoantigens than to alloantigens is possibly attributable to a stronger reaction of xenoreactive T cells; the interspecies incompatibility of CD47 may contribute to such xenoreactive CD4 + T cell responses via an indirect pathway.