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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4320-4327.
Prepublished online as a Blood First Edition Paper on February 6, 2007; DOI 10.1182/blood-2006-11-053769.
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Submitted November 6, 2006
Accepted January 16, 2007
DC-HIL is a negative regulator of T lymphocyte activation
Jin-Sung Chung, Kota Sato, Irene I. Dougherty, Ponciano D. Cruz Jr., and Kiyoshi Ariizumi*
The University of Texas Southwestern Medical Center, & Dermatology Section (Medical Service), Dallas Veterans Affairs Medical Center, Dallas, TX, United States
* Corresponding author; email: kiyoshi.ariizumi{at}utsouthwestern.edu.
T cell activation is the net product of competing positive and negative signals transduced by regulatory molecules on antigen presenting cells (APC) binding to corresponding ligands on T cells. Having previously identified DC-HIL as a receptor expressed by APC that contains an extracellular immunoglobulin-like domain, we postulated that it plays a role in T cell activation. To probe this function, we created soluble recombinant DC-HIL, which we observed to bind activated (but not resting) T cells, indicating that expression of the putative ligand on T cells is induced by activation. Binding of DC-HIL to T cells attenuated these cells' response to anti-CD3 antibody, curtailing IL-2 production, and preventing entry into the cell cycle. By contrast, addition of soluble DC-HIL to either allogeneic or ovalbumin-specific lymphocyte reactions augmented T cell proliferation, and its injection into mice during the elicitation (but not sensitization) phase of contact hypersensitivity exacerbated ear swelling responses. Mutant analyses showed the inhibitory function of DC-HIL to reside in its extracellular Ig-like domain. We conclude that endogenous DC-HIL is a negative regulator of T lymphocyte activation and this native inhibitory function can be blocked by exogenous DC-HIL, leading to enhanced immune responses.
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