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An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4⁺CD25⁺ T Regulatory Cells¹

Transplant Research Division, University Health Network, Toronto, Ontario, Canada

In previous studies we reported that while interaction between the relatively ubiquitously expressed molecule CD200 and one of its receptors, CD200R1, resulted in direct suppression of alloreactivity, engagement of alternate receptors led instead to altered differentiation of dendritic cells (DCs) from marrow precursors, which could in turn foster development of Foxp3⁺ regulatory T cells. We have explored this effect of engagement of alternate receptors by using a monoclonal agonist Ab to CD200R2 and investigating expression of TLRs on DCs induced in vivo and in vitro after CD200 stimulation in mice in which the gene encoding CD200R1 was deleted. CD200 stimulation was achieved by using either a soluble form of CD200 (CD200Fc) or overexpression of CD200 as a doxycycline-inducible transgene. Although broadly similar effects were seen, consistent with the hypothesis that triggering of CD200R2 does produce DCs with a characteristic TLR repertoire, there are subtle differences in suppression of alloreactivity achieved by CD200 delivered in these two manners, which is consistent with a complexity of CD200:CD200R engagement not previously appreciated.

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 Heart and Stroke association of Ontario.

² Address correspondence and reprint requests to Dr. R. Gorczynski, Room 2-805, MaRS Tower, 101 College Street, Toronto, Ontario, Canada M5G 1L7. E-mail address: reg.gorczynski{at}utoronto.ca

³ Abbreviations used in this paper: DC, dendritic cell; F10, alpha minimal essential medium with 10% FCS; BMDC, bone marrow-derived DC; CypA, cyclophilin A; PGN, peptidoglycan; RpL13A, ribosomal protein L13a; Treg, regulatory T cells; wt, wild type.