Acute rejection in the absence of cognate recognition of allograft by T cells.
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.
Braun
M Y
MY
Laboratory of Experimental Immunology and Department of Histopathology, Université Libre de Bruxelles, Brussels, Belgium. mbraun@ulb.ac.be
Grandjean
I
I
Feunou
P
P
Duban
L
L
Kiss
R
R
Goldman
M
M
Lantz
O
O
D000208:Acute Disease; D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006183:H-2 Antigens / Q000276:immunology; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012737:Sex Factors; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse