Loss of epidermal integrity by T cell-mediated attack induces long-term local resistance to subsequent attack. I. Induction of resistance correlates with increases in Thy-1+ epidermal cell numbers.

Abstract

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.

Induction and control of lichenoid tissue reactions

“…In fact, various in vitro studies have shown that stimuli known to increase HSP synthesis and treatment with TNF or IFN-3, render target cells resistant to subsequent attack by cytolytic T cells, NK cells or TNF [37,72]. Although the mechanisms underlying the resistance against killing remain unclear, we have recently provided evidence indicating the presence of a locally acting suppressor mechanism by which the integrity of the epidermal structures can be protected from an autoimmune attack by T cells [51].…”

Epidermal T lymphocytes ? ontogeny, features and function

“…Recently, Shiohara et al [72] have proposed that one of the functions of DETC is to protect the epidermis against damage by autoreactive T cells. This concept was based on the observations that (i) the epidermis of mice that had recovered from graft versus host disease (GVHD) contains much higher numbers of Thy-1 + cells than normal mice, and (ii) that these Thy-1 + cells protect the epidermis against a second attack of GVHD effector T cell clones.…”

Analysis of the T cell receptor Vγ region gene repertoire in bronchoalveolar lavage (BAL) and peripheral blood of atopic asthmatics and healthy subjects

“…In healthy subjects, about 90% of blood T lymphocytes express a TCR composed of -and -chains that collectively recognize a broad range of antigens [14]. ÿ CD8 phenotype, provide a regulatory role over the T cell effector subset [15][16][17][18][19][20][21][22]. However, the role of T lymphocytes in the human lung or airways [23] is not yet known.…”

“…T lymphocytes play a role in asthma [32]; (ii) T cells seem to regulate such T cells in a number of typically T cell-mediated conditions [15][16][17][18][19][20][21][22]; (iii) T cell subsets home in the epithelial surface [23,33], of several species; (iv) one of the most important ligands T cells respond to are hsp [34]; (v) hsp have been shown to be up-regulated in the stable asthmatic airway epithelium [35] or following allergen challenge [36]; and (vi) genetic linkage has been reported between the = loci and atopy [37].…”