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Updated: Aug 18, 2026

Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
CD4+ T cells responsive through the indirect pathway can mediate skin graft rejection in the absence of
1Department of Medicine, Case Western Reserve University, and the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Ohio 44106, USA.
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.
Conclusion:
CD4+ T cells recognizing alloantigens via the indirect pathway can mediate skin graft rejection in the absence of IFN-gamma.
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