CD8+ T cell subsets Tc1 and Tc2 cause different histopathologic forms of murine cardiac allograft rejection

Background. CD4(+) T cell effector function is sufficient to mediate allograft rejection, and it is suggested that CD8(+) T cell-mediated effects are dependent on CD4(+) T cell help. CD8(+) T cells can be classified into at least two functional subsets: Tc1, producing high amounts of interferon (IFN) -gamma and Tc2, producing interleukin (IL)-4, -5, -10, and -13 and low levels of IFN-gamma, Because these subsets express different chemokine receptors, they may have different capabilities of migrating into grafts. Once in the graft, each subset may perform different effector functions dependent on the cytokines it produces. We asked whether allospecific CD8(+) T cells, in the absence of CD4(+) T cells, are capable of mediating rejection of a primarily vascularized allograft, and if Tc1 and Tc2 cells differ in their ability to mediate rejection. Methods. Hearts from H-2(d) mice were transplanted into H-2(b) RAG 1-/- recipients. Without manipulation, these fully mismatched allografts would survive indefinitely due to the absence of mature T and B cells. We adoptively transferred allo-(H-2(d))- reactive Tc1 or Tc2 cells from H-2b mice into each recipient. Grafts were harvested and analyzed on predefined timepoints, rejection was graded on a modified ISHLT scale. Results, On day 7, grafts from Tc1- or Tea-injected animals showed grade 1-2 parenchymal rejection with stable phenotype and comparable distribution of graft infiltrating CD8+ T cells. Adoptive transfer of IFN-gamma (high) Tc1, but not of IFN-gamma (low) Tc2 cells was followed by the development of graft vasculitis, as well as graft arteriopathy. Adoptive transfer of IL-4(high) IL-5(high) Tc2, but not of IL-4(low) IL-5(low) Tc1 cells lead to extensive infiltration of eosinophils and formation of giant cells. Conclusions. Both Tc1 and Tc2 cells can mediate murine cardiac allograft rejection in the absence of CD4(+) T cell help, although each subset elicits a different type of inflammatory response. In this model, cytokine secretion of either functional CD8(+) T effector cell subset is an important effector mechanism in the process of allograft rejection: IFN-gamma (high) Tc1 cells are important in early graft vasculitis, although IL-4(high) IL-5(high) Tc2 cells promote recruitment of secondary effecters like eosinophils.