Cloned auto-Ia-reactive T cells elicit lichen planus-like lesion in the skin of syngeneic mice
Saito, K.; Tamura, A.; Narimatsu, H.; Tadakuma, T.; Nagashima, M.
Journal of Immunology 137(8): 2485-2495
1986
ISSN/ISBN: 0022-1767 PMID: 2944957 Document Number: 277016
To explore the physiologic or pathologic roles of autoreactive T cells, we examined immunological functions of several autoreactive mouse T cell clones in vitro and in vivo. All of the T cells clones were Lyt-2-, L3T4+ and showed self-I region-restricted proliferative responses (one clone was self-I-E restricted, the other clones were self-I-A restricted). One clone derived from C57BL/6 mouse and reactive to the self-I-Ab product (clone bb1-2) showed cross-reactivity to the I-Ak product. Among four such auto-Ia-reactive T cell clones examined, one clone produced fairly large amounts of interleukin 2 (IL 2) in response to syngeneic stimulator cells, and mediated help for the in vitro cytotoxic T cell (CTL) responses of syngeneic thymocytes, whereas this clone did not mediate in vitro antibody responses of syngeneic B cells. The other three clones were producers of small amounts of IL 2 and did not mediate the in vitro CTL responses. Among the three clones, clone bb1-2 showed strong regulatory function, and clone kk-1 (B10.BR origin and self-I-Ak reactive) showed weak regulatory function in in vitro antibody responses of syngeneic B cells. The physiologic or pathologic roles of autoreactive T cells in vivo were explored by injecting subcutaneously clone kk-1 T cells or clone bb1-2 T cells into the footpads of the respective syngeneic mice. Clone kk-1 T cells injected into syngeneic mice elicited swelling of the footpad and marked accumulation of mononuclear cells in the dermis, leaving the epidermis intact, as in the delayed-type hypersensitivity reaction. As a notable finding, clone bb1-2 T cells injected into syngeneic mice elicited marked swelling of the footpad and lichen planus-like skin lesions, i.e., infiltration of lymphocytes in the epidermis and epidermal cell damage. The lymphocytes infiltrating in the epidermis were evaluated, as were the injected clone bb1-2 T cells expressing the Lyt-1.2 phenotype, by examination of the skin lesions elicited in C3H/He mice (H-2k, Lyt-1.1, 2.1) by the clone T cells. Clone bb1-2 T cells exerted in vitro cytotoxicity against H-2b and H-2k target cells, whereas clone kk-1 T cells did not show any cytotoxic activity, indicating a correlation between the cytotoxic activity of clone bb1-2 T cells and their ability to elicit lichen planus-like lesions. Injection of clone bb1-2 T cells, but not clone kk-1 T cells, into the skin of syngeneic mice induced expression of Ia antigen in a large number of epidermal keratinocytes. From these results, we hypothesized the processes in development of lichen planus-like skin lesions by injection of auto-Ia-reactive clone bb1-2 T cells, and we discuss the pathogenetic significance of autoreactive T cells in lichen planus, which is suspected to be an autoimmune disease.