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,
*
Laboratory of Experimental Immunology and
Department of Histopathology, Université Libre de Bruxelles, Brussels, Belgium;
Institut National de la Santé et de la Recherche Médicale, Unité 25, Hôpital Necker, Paris, France; and
Laboratoire d’Immunologie, Institut Curie, Paris, France
We studied the effects of the indirect pathway of allograft
recognition using T cells from TCR transgenic Marilyn mice, which
recognize the male Ag H-Y in an I-Ab-restricted fashion.
The T cells are not alloreactive to the H-2k haplotype,
because they are not activated when adoptively transferred into
recombinase-activating gene-2-/- common
-chain-/- double-mutant H-2k male or
female mice. However, skin from H-2k males, but not from
H-2k females, is acutely rejected by recombinase-activating
gene-2-/- transgenic female recipients. In vitro, Marylin
spleen cells primed by H-2k skin grafting proliferated and
secreted both IL-4 and IFN- in response to H-2k male
stimulators. However, the removal of H-2b APC from the
responding population abolished the response. Taken together, these
results show that the indirect recognition that triggers rejection in
this model is due to the recognition of H-Y Ag shed from
H-2k male allograft and presented by the recipient’s own
I-Ab APC to transgenic T cells. This study demonstrates
unequivocally the capacity of naive CD4+ T cells to promote
the rejection of allografts through mechanisms that involve indirect
destruction of grafted tissues.
This article has been cited by other articles:
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