Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes.
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-alpha 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.
Tahara
Hiroyuki
H
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ide
Kentaro
K
Basnet
Nabin
N
Tanaka
Yuka
Y
Ohdan
Hideki
H
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D015478:Antigens, Heterophile; D051928:CD47 Antigen; D007519:Isoantigens; D011993:Recombinant Fusion Proteins