Submitted June 20, 2006
Accepted December 26, 2006
FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV-1 infection
Timothy J Wilson, Rachel M Presti, Ilaria Tassi, Edgar T Overton, Marina Cella, and Marco Colonna*
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States
Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, United States
* Corresponding author; email: mcolonna{at}pathology.wustl.edu.
Fc receptor like proteins (FcRLs) are a growing family of molecules homologous to Fc
RI. Whereas all seven previously reported Fc receptor homologs are expressed by B cells, here we report a new receptor, FcRL6, that is expressed by cytolytic cells including 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 impacts on cytokine secretion. However, FcRL6 expression among T lymphocytes is greatly expanded in HIV-1 infected individuals, and includes not only effector and effector-memory CD8+ T cells but also populations of CD4+ T cells. Expansion 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.
