RESUMO
8-Methoxypsoralen plus UVA (PUVA) photochemotherapy is an effective treatment for many skin diseases including psoriasis. However, its exact mechanism of therapeutic action is incompletely understood. Previously, in K5.hTGFß1 transgenic psoriatic mice, we found that PUVA induces Foxp3+ CD25+ CD4+ regulatory T cells in both lymph node and spleen. Now, in the same model, we investigated whether cutaneous lymphocyte-associated antigen (CLA) mediates PUVA's effect on homing of CD25+ CD4+ T cells to the lymph nodes of K5.hTGFß1 transgenic mice. We found that a low dose of topical PUVA maximally increased the proportion of CLA + CD25+ CD4 + T cells in the lymph nodes by up to 8-fold. We also observed an increased number of Foxp3+ CD25+ T cells in the skin of the mice after PUVA treatment. Together, these findings suggest that PUVA affects the homing of regulatory T cells.
Assuntos
Linfonodos/citologia , Metoxaleno/administração & dosagem , Terapia PUVA , Fármacos Fotossensibilizantes/administração & dosagem , Psoríase/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Animais , Antígenos de Diferenciação de Linfócitos T/efeitos dos fármacos , Antígenos de Diferenciação de Linfócitos T/efeitos da radiação , Modelos Animais de Doenças , Subunidade alfa de Receptor de Interleucina-2/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-2/efeitos da radiação , Linfonodos/efeitos dos fármacos , Linfonodos/efeitos da radiação , Camundongos , Camundongos Transgênicos , Psoríase/imunologia , Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/efeitos da radiaçãoRESUMO
The differentiation of plaque-forming cell (PFC) precursors against bromelain-treated syngeneic erythrocytes (Br MRBC) into PFC induced in vitro by LPS is down-regulated by nylon non-adherent (nylon-passed--NP) T cells and by nylon adherent (NA) T cells. NA T cells are more potent inhibitors than NP T cells. This regulatory activity of NA and NP T cells results from an interaction between CD4+ radioresistant and CD8+ radiosensitive T cells. Furthermore CD4+ T cells from the NA fraction but not from the NP fraction are activated cells: their inhibitory activity is abrogated after preincubation with cycloheximide. These results are discussed within the overall framework of T-cell regulation of autoimmune anti-Br MRBC B-cell subsets.