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Ly6C^low Monocytes Differentiate into Dendritic Cells and Cross-Tolerize T Cells through PDL-1¹

YuFeng Peng^*, Yvette Latchman^, and Keith B. Elkon^2,*,

^* Division of Rheumatology and Department of Immunology, University of Washington, Seattle, WA 98195; Puget Sound Blood Center, Seattle, WA 98104; and Division of Hematology, University of Washington, Seattle, WA 98195

Monocyte-derived dendritic cells are active participants during the immune response against infection, but whether they play a role in maintaining self-tolerance under steady-state conditions is not known. Here we investigated the differentiation of monocytes, their ability to ingest apoptotic cells, and their potential functionality in vivo. We observed that Ly6C (Gr-1)^low mature monocytes up-regulate their MHC II level in the spleen, express high levels of PDL-1 (programmed death ligand 1), and are more efficient than Ly6C^high immature monocytes in the ingestion of apoptotic cells in vivo. Sorted circulating Ly6C^low monocytes were able to cross-present both apoptotic cell-associated OVA and soluble OVA protein. Monocytes containing apoptotic cells can further differentiate into CD11c⁺CD8^–MHC II⁺ splenic dendritic cells that maintained high expression of PDL-1. Since wild-type but not PDL-1-deficient peripheral blood monocytes containing apoptotic cell-associated OVA suppressed the response to OVA immunization, PDL-1 expression was required for monocyte-mediated T cell tolerance. These observations demonstrate that Ly6C^low mature monocytes can promote tolerance to self Ag contained in apoptotic cells through a PDL-1-dependent mechanism.

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 National Institutes of Health Grant AR48796 (to K.B.E.). Y.F.P. was supported in part by a Career Development Grant from the Arthritis Foundation.

² Address correspondence and reprint requests to Dr. Keith B. Elkon, Division of Rheumatology, University of Washington, 1959 NE Pacific Street, Box 356428, Seattle, WA 98195. E-mail address: elkon{at}u.washington.edu

³ Abbreviations used in this paper: DC, dendritic cell; Apo, apoptotic cell; PDL, programmed death ligand.

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