Y. Zhao et al., PIG MHC MEDIATES POSITIVE SELECTION OF MOUSE CD4(-CELLS WITH A MOUSE MHC-RESTRICTED TCR IN PIG THYMUS GRAFTS() T), The Journal of immunology (1950), 161(3), 1998, pp. 1320-1326
Remarkably normal immune function and specific T cell tolerance to dis
cordant xenogeneic donors can be achieved by grafting fetal pig thymus
and liver (FP THY/LIV) tissue to T cell and NK cell-depleted, thymect
omized (ATX) mice. To determine whether or not host class II MHC molec
ules participate in the positive selection of mouse CD4(+) T cells in
FP THY/LIV grafts, ne compared their development in ATX, ''AND'' TCR-t
ransgenic mice with positive selecting or nonselecting host MHC genoty
pes, Mouse TCR-transgenic CD4 single positive T cells repopulated the
periphery significantly and to a similar extent in both T/NK cell-depl
eted, ATX AND mice with positive-selecting or nonselecting MHC backgro
unds after grafting with FP THY/LIV. Therefore, MHC molecules from a w
idely disparate xenogeneic species can positively select T cells beari
ng a host class II MHC-restricted TCR without a contribution from the
host MHC. These results, in combination with previous studies performe
d in this model, suggest that the T cell repertoire that is generated
by the combination of positive selection on xenogeneic MHC and negativ
e selection on both recipient and xenogeneic porcine MHC is tolerant o
f both donor and recipient and has sufficient cross-reactivity with ho
st MHC/foreign peptide complexes to confer a high level of immunocompe
tence. The results hale implications for the potential clinical applic
ability of xenogeneic thymic transplantation and also suggest a predom
inant role for the TCR recognition of species-conserved MHC residues i
n positive selection.