CD4+ T cells responsive through the indirect pathway can mediate skin graft rejection in the absence of interferon-gamma.
BACKGROUND
T cells responding through the indirect pathway can induce allograft rejection, but mechanisms of rejection are not known. Interferon-y (IFN-gamma) may be an important mediator of rejection under these circumstances.


METHODS
We transferred CD4+ T cells from IFN-gamma-deficient (IFN-gamma-/-) mice into SCID recipients of MHC II-deficient (MHC II-/-) skin grafts. Under these conditions, rejection can only occur via the indirect pathway and cannot be mediated by T-cell production of IFN-gamma.


RESULTS
IFN-gamma-/- CD4+ T cells rejected MHC II -/- skin grafts. Flow cytometry revealed only CD4+ T cells in the recipients. Cytokine enzyme-linked immunosorbent spot assays confirmed only indirect recognition with an associated expansion of an alloreactive population of IL-2-, IL-4-, and IL-5-secreting T cells.


CONCLUSIONS
CD4+ T cells recognizing alloantigens via the indirect pathway can mediate skin graft rejection in the absence of IFN-gamma.
Valujskikh
A
A
Department of Medicine, Case Western Reserve University, and the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Ohio 44106, USA.
Heeger
P S
PS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000503:physiopathology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000172:deficiency; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D016038:Skin Transplantation
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma