This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 2007-0237OCv1 38/2/161    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 Naito, T. Articles by Nakamura, H. Search for Related Content PubMed PubMed Citation Articles by Naito, T. Articles by Nakamura, H.

Lung Dendritic Cells Have a Potent Capability to Induce Production of Immunoglobulin A

¹ Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence and requests for reprints should be addressed to Takafumi Suda, M.D., Ph.D., Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine,1-20-1 Handayama, Higashiku, Hamamatsu, 431-3192, Japan. E-mail: suda{at}hama-med.ac.jp

The mucosal immune system provides the first line of defense against inhaled pathogens in the lung. This system is largely mediated by immunoglobulin A (IgA) locally produced by plasma cells, which originate from homing IgA-committed B cells. It has not been determined what types of antigen-presenting cells (APCs) primarily induce B cell differentiation for IgA production in the lung. In addition, although mucosal dendritic cells (DCs) are functionally distinct from DCs in other tissues, it is unclear whether IgA-inducing capability differs between mucosal lung DCs (LDCs) and nonmucosal DCs. The present study was conducted to identify APCs principally responsible for IgA induction in the lung, and to determine potential differences in IgA-inducing capacity between LDCs and nonmucosal DCs. We measured immunoglobulin and cytokine production in a coculture system containing naive IgD⁺ B cells, naive T cells from ovalbumin-specific T cell–receptor transgenic mice, and APCs including LDCs, alveolar macrophages (AMs), or spleen DCs (SDCs). LDCs induced significantly greater levels of IgA, IgG1, IL-6, and TGF-β than AMs and SDCs, whereas no differences were found in the production of IgM or IgG2a. In addition, the IgA percentage of total class-switched immunoglobulin was highest in cocultures with LDCs (38.4%) when compared with those with AMs (15.1%) and SDCs (22.7%). Neutralizing TGF-β, but not IL-6, significantly decreased IgA induction by LDCs and SDCs, but not by AMs. This study suggests that LDCs are the primary APCs introducing IgA to the lung, and have a more potent IgA-inducing capacity than nonmucosal DCs.

Key Words: immunoglobulin A • lung dendritic cell • alveolar macrophage • TGF-β • interleukin-6

CLINICAL RELEVANCE Our study demonstrates that lung dendritic cells are the principal antigen-presenting cells introducing immunoglobulin (Ig)A to the lung, and that they have a more potent capacity to induce IgA production than nonmucosal dendritic cells.

 

This article has been cited by other articles:

				Y. Ozawa, T. Suda, T. Nagata, D. Hashimoto, Y. Nakamura, N. Enomoto, N. Inui, Y. Koide, H. Nakamura, and K. Chida Mucosal Vaccine Using CTL Epitope-Pulsed Dendritic Cell Confers Protection for Intracellular Pathogen Am. J. Respir. Cell Mol. Biol., October 1, 2009; 41(4): 440 - 448. [Abstract] [Full Text] [PDF]