RESUMO
CD4(+)CD25(+) regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-beta (TGF-beta) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4(+)CD45RB(high) T cells that express a dominant negative TGF-beta receptor type II (dnTbetaRII) and therefore cannot respond to TGF-beta, escape control by T reg cells in vivo. CD4(+)CD25(+) T reg cells from the thymus of dnTbetaRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-beta is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTbetaRII CD4(+)CD25(+) population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4(+)CD25(+) T reg cells develop normally in the absence of TGF-beta1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-beta1(-/-) T reg cells was abrogated by anti-TGF-beta monoclonal antibody, indicating that functional TGF-beta can be provided by a non-T reg cell source.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Tolerância Imunológica/imunologia , Receptores de Interleucina-2/metabolismo , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Diferenciação Celular , Colite/imunologia , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Camundongos , Camundongos Knockout , Receptores de Interleucina-2/imunologia , Baço/imunologia , Baço/metabolismo , Células Th1/citologia , Células Th1/metabolismo , Timo/imunologia , Timo/metabolismo , Fator de Crescimento Transformador beta/deficiência , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1RESUMO
The case is reported of a 26-y-old woman with latent Lyme borreliosis that was concurrently activated with a herpes simplex virus type 1 infection. Immune suppression by stress may have caused activation of both infections.