RESUMEN
Both ultraviolet (UV) irradiation and cis-urocanic acid (UCA) are reported to be associated with the suppression of contact hypersensitivity (CHS) and the induction of a soluble factor which suppresses leukocyte adherence inhibition (LAI) assays in vitro. The cellular origin of the suppressor factor (SF) has now been investigated in vivo and in vitro, using monoclonal antibodies against lymphocyte surface markers to deplete certain cell populations, namely T lymphocytes bearing the L3T4 (helper) and Lyt-2 (suppressor) markers. Depletion of Lyt-2+ cells from irradiated mice in vivo and from spleen cell cultures in vitro led to the elimination of detectable levels of SF. Depletion of L3T4+ cells had no such effect. Similarly, Lyt-2+ cells (but not L3T4+ cells) were shown to be necessary for the production of SF by normal spleen cells cultured with cis-UCA. These data suggest that the production of SF following UV irradiation may be related to the action of cis-UCA on Lyg-2+ lymphocytes.
Asunto(s)
Factores Supresores Inmunológicos/inmunología , Subgrupos de Linfocitos T/inmunología , Ácido Urocánico/farmacología , Animales , Anticuerpos Monoclonales , Linfocitos T CD4-Positivos/inmunología , Dermatitis por Contacto/inmunología , Técnicas In Vitro , Prueba de Inhibición de Adhesión Leucocitaria , Ratones , Rayos UltravioletaRESUMEN
Cis-urocanic acid (cis-UCA), produced from trans-UCA (a normal component of epidermis) by UV irradiation, suppressed cell-mediated immunological reactions in vivo and in vitro. It suppressed the development of contact hypersensitivity (CHS) when injected into mice, and it suppressed leucocyte adherence inhibition (LAI) reactions of previously sensitized lymphocytes exposed to antigen. Serum from mice injected with cis-UCA was also immunosuppressive in vitro. Normal murine spleen cells cultured with cis-UCA produced a non-dialysable factor which suppressed LAI reactivity. Trans-UCA was ineffectual in all of these systems. Both the ability of cis-UCA to induce an immunosuppressive serum factor and its ability to suppress CHS were abrogated by prior administration of cyclophosphamide, indicating that cis-UCA (normally from irradiated epidermis) stimulates T suppressor cells to produce the previously described suppressor factor in serum and the immunosuppression associated with short-term irradiation.
Asunto(s)
Dermatitis por Contacto/inmunología , Imidazoles/farmacología , Tolerancia Inmunológica/efectos de la radiación , Rayos Ultravioleta , Ácido Urocánico/farmacología , Animales , Ciclofosfamida/farmacología , Tolerancia Inmunológica/efectos de los fármacos , Prueba de Inhibición de Adhesión Leucocitaria , Ratones , Ácido Urocánico/antagonistas & inhibidoresRESUMEN
Serum from UV-irradiated mice was shown to be immunosuppressive in vitro and in vivo. It suppressed leucocyte adherence inhibition reactions of cells from sensitized syngeneic and allogeneic mice, and suppressed the development of contact hypersensitivity after passive transfer to mice. Supernatants of cultures of spleen cells from irradiated mice were also suppressive. The suppressive factors in sera and culture supernatants were non-dialysable. The suppressive effect of UV irradiation was abrogated by cyclophosphamide, but this restored reactivity was still inhibited by serum from irradiated donors; this suggests that the serum factor requires T suppressor cells for its production but not for its action. The level of interleukin 1 (IL-1) was not raised in serum from UV-irradiated mice; thus the serum factor appears not to be IL-1.
Asunto(s)
Dermatitis por Contacto/inmunología , Tolerancia Inmunológica/efectos de la radiación , Animales , Sangre , Ciclofosfamida/farmacología , Femenino , Tolerancia Inmunológica/efectos de los fármacos , Prueba de Inhibición de Adhesión Leucocitaria , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Bazo/inmunología , Rayos UltravioletaRESUMEN
BALB/c mice subjected to a single dose of UV-B radiation showed suppressed contact hypersensitivity to trinitrochlorobenzene. The in vitro antigen reactivity of peritoneal cells from these mice was investigated using the leucocyte-adherence inhibition assay. These cells showed a high degree of reactivity with specific antigen. However, this reactivity, but not the reactivity of cells from non-irradiated sensitized mice, could be suppressed by serum from UV-treated sensitized mice. The suppressive effect of this serum could also be demonstrated on other syngeneic systems with unrelated antigens and was partially effective with allogeneic cells, indicating a lack of antigen specificity and genetic restriction. Suppressive properties were also found in serum taken from mice 3-5 days (but not at other times) after irradiation without subsequent sensitization.