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CD2 Distinguishes Two Subsets of Human Plasmacytoid Dendritic Cells with Distinct Phenotype and Functions¹

Toshimichi Matsui^2,*, John E. Connolly^2,*, Mark Michnevitz^2,*, Damien Chaussabel^*, Chun-I Yu^*,, Casey Glaser^*, Sasha Tindle^*, Marc Pypaert^3,, Heidi Freitas^*, Bernard Piqueras^*, Jacques Banchereau^4,* and A. Karolina Palucka^4,*

^* Baylor-National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense and Institut National de la Santé et de la Médicale Unité 899, Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204; Institute of Biomedical Studies, Baylor University, Waco, TX 76798; and Yale University School of Medicine, New Haven, CT 06520

Plasmacytoid dendritic cells (pDCs) are key regulators of antiviral immunity. They rapidly secrete IFN- and cross-present viral Ags, thereby launching adaptive immunity. In this study, we show that activated human pDCs inhibit replication of cancer cells and kill them in a contact-dependent fashion. Expression of CD2 distinguishes two pDC subsets with distinct phenotype and function. Both subsets secrete IFN- and express granzyme B and TRAIL. CD2^high pDCs uniquely express lysozyme and can be found in tonsils and in tumors. Both subsets launch recall T cell responses. However, CD2^high pDCs secrete higher levels of IL12p40, express higher levels of costimulatory molecule CD80, and are more efficient in triggering proliferation of naive allogeneic T cells. Thus, human blood pDCs are composed of subsets with specific phenotype and functions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Baylor Health Care Systems Foundation and the National Institutes of Health (U19 AIO57234 and CA78846 to J.B.). J.B. is the recipient of the Caruth Chair for Transplantation Immunology Research. A.K.P. is the recipient of the Michael A. Ramsay Chair for Cancer Immunology Research.

² T.M., J.E.C., and M.M. contributed equally.

³ M.P. passed away in 2008.

⁴ Address correspondence and reprint requests to Dr. A. Karolina Palucka and Dr. Jacques Banchereau, Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204. E-mail addresses: karolinp{at}baylorhealth.edu and jacquesb{at}baylorhealth.edu

⁵ Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DC; mDC, myeloid DC; SLE, systemic lupus erythematosus.

⁶ The online version of this article contains supplemental material.

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The JI 2009 182: 6631-6632. [Full Text]