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Acute Rejection in the Absence of Cognate Recognition of Allograft by T Cells¹

Michel Y. Braun^2,*, Isabelle Grandjean, Pascal Feunou^*, Livine Duban, Robert Kiss, Michel Goldman^* and Olivier Lantz^,

^* 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-A^b-restricted fashion. The T cells are not alloreactive to the H-2^k haplotype, because they are not activated when adoptively transferred into recombinase-activating gene-2^-/- common -chain^-/- double-mutant H-2^k male or female mice. However, skin from H-2^k males, but not from H-2^k females, is acutely rejected by recombinase-activating gene-2^-/- transgenic female recipients. In vitro, Marylin spleen cells primed by H-2^k skin grafting proliferated and secreted both IL-4 and IFN- in response to H-2^k male stimulators. However, the removal of H-2^b 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-2^k male allograft and presented by the recipient’s own I-A^b 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.

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