| First Author | Gereke M | Year | 2009 |
| Journal | Am J Respir Crit Care Med | Volume | 179 |
| Issue | 5 | Pages | 344-55 |
| PubMed ID | 19096007 | Mgi Jnum | J:165000 |
| Mgi Id | MGI:4835868 | Doi | 10.1164/rccm.200804-592OC |
| Citation | Gereke M, et al. (2009) Alveolar type II epithelial cells present antigen to CD4(+) T cells and induce Foxp3(+) regulatory T cells. Am J Respir Crit Care Med 179(5):344-55 |
| abstractText | RATIONALE: Although the contribution of alveolar type II epithelial cells (AECIIs) in respiratory immunity has become increasingly appreciated, their precise function in the induction and regulation of T-cell reactivity to self-antigen remains poorly understood. OBJECTIVES: To investigate the role of AECII in the initiation of T-cell reactivity to alveolar self-antigen, and to clarify their function in the peripheral induction of Foxp3(+) regulatory CD4(+) T cells. METHODS: To dissect the complex cellular and molecular functions of AECIIs in lung inflammation and immune regulation, we use a transgenic mouse model for CD4(+) T-cell-mediated pulmonary inflammation. MEASUREMENTS AND MAIN RESULTS: Here we report that AECIIs present endogenously expressed antigen on major histocompatibility complex class II molecules to CD4(+) T cells. Epithelial antigen display was sufficient to induce primary T-cell activation and pulmonary inflammation. Upon inflammation, AECIIs induce the differentiation of Foxp3(+) regulatory T cells by a mechanism involving antiproliferative soluble factors, including transforming growth factor (TGF)-beta. Whereas, in acute inflammation, TGF-beta appears to be the dominant factor to induce regulatory T cells, other AECII-derived factors can substitute for and/or synergize with TGF-beta in chronic pulmonary inflammations. CONCLUSIONS: AECIIs are capable of priming naive CD4(+) T cells, demonstrating an active participation of these cells in respiratory immunity. Moreover, AECIIs display as yet unrecognized functions in balancing inflammatory and regulatory T-cell responses in the lung by connecting innate and adaptive immune mechanisms to establish peripheral T-cell tolerance to respiratory self-antigen. |
