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

• Published in: The Journal of immunology (1950) 2001-04, Vol.166 (8), p.4879-4883
• Main Authors: Braun, Michel Y, Grandjean, Isabelle, Feunou, Pascal, Duban, Livine, Kiss, Robert, Goldman, Michel, Lantz, Olivier
• Format: Article
• Language: English
• Subjects: Acute Disease; Adoptive Transfer; Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Epitopes, T-Lymphocyte - immunology; Female; Graft Rejection - genetics; Graft Rejection - immunology; Graft Rejection - pathology; H-2 Antigens - immunology; histocompatibility antigen H-2; Immunophenotyping; Interphase - immunology; Lymphocyte Activation; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Molecular Sequence Data; Sex Factors; Skin Transplantation - immunology; Skin Transplantation - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; Transplantation, Homologous
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.8.4879

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 gamma-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-gamma 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.