This Article Full Text Full Text (PDF) Online Supplement Editorial: Farrah Kheradmand, Amarbir Singh Mattewal, David B. Corry All Versions of this Article: 200804-592OCv1 179/5/344    most recent Alert me when this article is cited Alert me if a correction is posted Services Related articles in AJRCCM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gereke, M. Articles by Bruder, D. Search for Related Content PubMed PubMed Citation Articles by Gereke, M. Articles by Bruder, D.

Alveolar Type II Epithelial Cells Present Antigen to CD4⁺ T Cells and Induce Foxp3⁺ Regulatory T Cells

¹ Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany; ² Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; and ³ Department of Medical Microbiology, University Hospital Essen, Essen, Germany

Correspondence and requests for reprints should be addressed to Dunja Bruder, Ph.D., Immune Regulation Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. E-mail: dunja.bruder{at}helmholtz-hzi.de

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)-β. Whereas, in acute inflammation, TGF-β appears to be the dominant factor to induce regulatory T cells, other AECII-derived factors can substitute for and/or synergize with TGF-β 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.

Key Words: peripheral tolerance • alveolar type II epithelial cells • immune regulation • autoimmunity • transgenic mouse model

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The contribution of type II alveolar epithelial cells (AECIIs) to respiratory immune regulation has become increasingly appreciated. However, their precise function in the induction and regulation of T-cell reactivity to self-antigens remains poorly understood. What This Study Adds to the Field We show here that major histocompatibility complex class II–expressing AECIIs present self-antigen to CD4+ T cells, resulting in functional activation of lung-reactive T cells. However, AECIIs also induce Foxp3+ regulatory T cells, thereby promoting lung tolerance.

 

Related articles in AJRCCM:

At Last, an Immune Organ We Can Call Our Own?

Farrah Kheradmand, Amarbir Singh Mattewal, and David B. Corry
AJRCCM 2009 179: 525-527. [Full Text]  

This article has been cited by other articles:

				R. H. Wilson, G. S. Whitehead, H. Nakano, M. E. Free, J. K. Kolls, and D. N. Cook Allergic Sensitization through the Airway Primes Th17-dependent Neutrophilia and Airway Hyperresponsiveness Am. J. Respir. Crit. Care Med., October 15, 2009; 180(8): 720 - 730. [Abstract] [Full Text] [PDF]

				F. Kheradmand, A. S. Mattewal, and D. B. Corry At Last, an Immune Organ We Can Call Our Own? Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 525 - 527. [Full Text] [PDF]