Induction of cutaneous graft-versus-host disease by local injection of unprimed T cells

Abstract

The skin is a major target organ in human graft-versus-host disease (GVHD) after bone-marrow transplantation. GVHD can be induced in mice by i.v. injection of T cells into unirradiated semi-allogeneic or lethally irradiated allogeneic recipients. However, in the murine systemic GVHD model, cutaneous lesions occur only in lethally irradiated recipients. Since lethal irradiation itself might induce the epidermal cell damage, several investigators have employed another murine model of cutaneous GVHD, in which cutaneous lesions were induced by intradermal injection of alloreactive T cell clones. Using this system, it has been reported that both MHC class I- and II-reactive T cell clones can induce cutaneous GVHD in non-irradiated or sublethally irradiated recipients. However, it has remained unknown whether or not freshly prepared T cells are able to induce cutaneous GVHD after local injection into non-irradiated recipients. We show that unprimed T cells can induce cutaneous GVHD after local injection into unirradiated MHC class II- or I + II-disparate recipients. In contrast to alloreactive T cell clones, unprimed T cells could elicit only mild cutaneous lesions in MHC class I-disparate recipients. Since sublethal irradiation of MHC class I-disparate recipients did not result in the manifestation of cutaneous lesions after injection of unprimed T cells, host anti-donor responses by radiosensitive cells could not be responsible for this phenomenon. This experimental system provides a useful model for analysis of the regulation mechanisms in the induction of GVHD by unprimed T cells.