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 Blood, 1 May 2007, Vol. 109, No. 9, pp. 3786-3793.
Prepublished online as a Blood First Edition Paper on January 9, 2007; DOI 10.1182/blood-2006-06-030023.

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IMMUNOBIOLOGY

FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV-1 infection

Timothy J. Wilson1, Rachel M. Presti1,2, Ilaria Tassi1, Edgar T. Overton2, Marina Cella1, and Marco Colonna1

1 Department of Pathology and Immunology and 2 Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St Louis, MO

Fc receptor–like proteins (FcRLs) are a growing family of molecules homologous to Fc{gamma}RI. Whereas all 7 previously reported Fc receptor homologs are expressed by B cells, here we report a new receptor, FcRL6, that is expressed by cytolytic cells including natural killer (NK) cells and effector and effector-memory CD8+ T cells. FcRL6 contains a novel cytoplasmic cysteine-rich motif and recruits SHP-2 through a phosphorylated ITIM, indicating a potential signaling function in effector lymphocytes. In vitro, FcRL6 does not greatly influence NK-cell or CD8+ T-cell–mediated cytotoxicity and has minimal impact on cytokine secretion. However, FcRL6 expression among T lymphocytes is greatly expanded in human immunodeficiency virus type 1 (HIV-1)–infected individuals, and includes not only effector and effector-memory CD8+ T cells but also populations of CD4+ T cells. Expansion of FcRL6-positive lymphocytes is not related to viral load, but is indicative of the dysregulated expansion of terminally differentiated effector lymphocyte populations in response to chronic HIV-1 infection and may serve as an important marker for chronic immune activation and for tracking the generation of effector cells following immune stimulation.


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