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CD27 Expression on CD4⁺ T Cells Differentiates Effector from Regulatory T Cell Subsets in the Lung¹

Douglas G. Mack^*, Allison M. Lanham^*, Brent E. Palmer^*, Lisa A. Maier^*, and Andrew P. Fontenot^2,*,

^* Department of Medicine and Department of Immunology, University of Colorado Denver, Aurora, CO 80045; and Department of Medicine, National Jewish Health, Denver, CO 80206

Beryllium exposure in the workplace can result in chronic beryllium disease, a granulomatous lung disorder characterized by CD4⁺ T cell alveolitis and progressive lung fibrosis. A large number of the CD4⁺ T cells recruited to the lung in chronic beryllium disease recognize beryllium in an Ag-specific manner and express Th1-type cytokines following T cell activation. Beryllium-responsive CD4⁺ T cells in the bronchoalveolar lavage (BAL) express an effector memory T cell phenotype and recognize beryllium in a CD28-independent manner. In this study, we show that the majority of beryllium-responsive CD4⁺ T cells in BAL have lost CD27 expression, whereas a subset of beryllium-responsive cells in blood retains expression of this costimulatory molecule. In addition, loss of CD27 on BAL CD4⁺ T cells inversely correlates with markers of lung inflammation. A small population of BAL CD4⁺ T cells retains CD27 expression, and these CD4⁺CD27⁺ T cells contain the FoxP3-expressing, naturally occurring regulatory T (T_reg) cell subset. Coexpression of CD27 and CD25 identifies the majority of FoxP3-expressing T_reg cells in blood and BAL, and these cells express potent suppressor function. Taken together, these findings suggest that CD27 is differentially expressed between effector T cells from the inflamed lung and can be used in conjunction with CD25 to isolate T_reg cells and assess their functional capacity in an ongoing adaptive immune response in a target organ.

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 Grants HL62410, ES011810, and AI050864 (to A.P.F.) and M01-RR00051 from the Division of Research Resources, General Clinical Research Center.

² Address correspondence and reprint requests to Dr. Andrew Fontenot, Division of Clinical Immunology (B164), University of Colorado Denver, 12700 East 19th Avenue, Aurora, CO 80045. E-mail address: andrew.fontenot{at}ucdenver.edu

³ Abbreviations used in this paper: CBD, chronic beryllium disease; BAL, bronchoalveolar lavage; BeS, beryllium-sensitized; BeSO₄, beryllium sulfate; T_EM cells, effector memory T; T_reg, regulatory T; SEB, staphylococcal enterotoxin B.