A Valujskikh1, P S Heeger. 1. Department of Medicine, Case Western Reserve University, and the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Ohio 44106, USA.
Abstract
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.
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.
Authors: Cavit D Kant; Yoshinobu Akiyama; Katsunori Tanaka; Susan Shea; Sarah E Connolly; Sharon Germana; Henry J Winn; Christian LeGuern; Georges Tocco; Gilles Benichou Journal: J Immunol Date: 2013-07-05 Impact factor: 5.422
Authors: Amar Singh; Sabarinathan Ramachandran; Melanie L Graham; Saeed Daneshmandi; David Heller; Wilma Lucia Suarez-Pinzon; Appakalai N Balamurugan; Jeffrey D Ansite; Joshua J Wilhelm; Amy Yang; Ying Zhang; Nagendra P Palani; Juan E Abrahante; Christopher Burlak; Stephen D Miller; Xunrong Luo; Bernhard J Hering Journal: Nat Commun Date: 2019-08-02 Impact factor: 14.919