Skin is known to be one of the worst affected target organs in graft-versus-host disease (GVHD)' (1). The cutaneous lesions are characterized by the epidermal cell death in association with a prominent T cell infiltrate (2). It is therefore thought that the cutaneous lesions occur as the result of a T cell-mediated immune attack on epidermal cells, either directly or via the release of various cytokines from the T cells, although the problem of whether the T cells toward the epidermal antigens cause these lesions has been still unclear (3). While much attention has been directed to effector T cells capable of mediating GVHD, almost nothing is known about the mechanism(s) by which the integrity oforgan structures can be protected from such a T cell-mediated immune attack in GVHD. This is due, in part, to a difficulty in producing experimental models of GVHD to be able to investigate the protection mechanism(s) .We have recently demonstrated that cutaneous GVHD, resembling lichen planus and lupus erythematosus in humans, can be induced in normal mice by intradermal inoculation into the footpads of cloned, autoreactive CD4+ T cells with cytolytic activity (4-6). The experimentally induced cutaneous GVHD is basically composed oftwo types of reactions: delayed-type hypersensitivity (DTH) reactions and epidermal cell damage defined histologically. DTH responses measurable by footpad swelling peaks at 24-48 h and then gradually recedes (5). Histologically, the DTH responses are characterized by the diffuse infiltration ofmononuclear cells and prominent edema in the dermis . In contrast, epidermal lesions characterized by the severe infiltration of T cells associated with the consequent epidermal cell damage reach maximum ' Abbreviations used in this paper: DTH, delayed-type hypersensitivity ; GVHD, graft-vs .-host disease; PLN, popliteal lymph node ; Thy-1 + EC, Thy-1 + epidermal cells. J. Exp. Men.

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We investigated the in vivo effect of recombinant interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) treatment of mice on the development of the delayed-type hypersensitivity (DTH) reaction and lichenoid tissue reaction (LTR) following the local injection of cloned autoreactive T cells. Both the DTH reaction and the LTR were significantly enhanced by pretreatment with IFN-gamma, but not with TNF-alpha. Induction of class II MHC antigens on keratinocytes was not essential for the enhancement by IFN-gamma. Administration of anti-IFN-gamma antibody reduced the DTH reaction and LTR, although complete inhibition was not observed with our treatment regimen. The ability of IFN-gamma to increase the number of the cloned T cells invading the epidermis in vivo, is in keeping with our previous observation that IFN-gamma treatment of cultured keratinocytes markedly increased the adherence reaction between T cells and keratinocytes in vitro.