DC-HIL is a negative regulator of T lymphocyte activation

Jin Sung Chung, Kota Sato, Irene I. Dougherty, Ponciano D Cruz, Kiyoshi Ariizumi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

T-cell activation is the net product of competing positive and negative signals transduced by regulatory molecules on antigen-presenting cells (APCs) binding to corresponding ligands on T cells. Having previously identified DC-HIL as a receptor expressed by APCs that contains an extracellular immunoglobulin (Ig)-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 naive T cells attenuated these cells' primary response to anti-CD3 antibody, curtailing IL-2 production, and preventing entry into the cell cycle. DC-HIL also inhibited reactivation of T cells previously activated by APCs (secondary response). 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 that this native inhibitory function can be blocked by exogenous DC-HIL, leading to enhanced immune responses.

Original languageEnglish (US)
Pages (from-to)4320-4327
Number of pages8
JournalBlood
Volume109
Issue number10
DOIs
StatePublished - May 15 2007

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T-cells
Lymphocyte Activation
Chemical activation
T-Lymphocytes
Antigen-Presenting Cells
Immunoglobulins
Ligands
Lymphocytes
Contact Dermatitis
Ovalbumin
Cell proliferation
Interleukin-2
Ear
Swelling
Anti-Idiotypic Antibodies
Cell Cycle
Cells
Cell Proliferation
Injections
Molecules

ASJC Scopus subject areas

  • Hematology

Cite this

DC-HIL is a negative regulator of T lymphocyte activation. / Chung, Jin Sung; Sato, Kota; Dougherty, Irene I.; Cruz, Ponciano D; Ariizumi, Kiyoshi.

In: Blood, Vol. 109, No. 10, 15.05.2007, p. 4320-4327.

Research output: Contribution to journalArticle

Chung, Jin Sung ; Sato, Kota ; Dougherty, Irene I. ; Cruz, Ponciano D ; Ariizumi, Kiyoshi. / DC-HIL is a negative regulator of T lymphocyte activation. In: Blood. 2007 ; Vol. 109, No. 10. pp. 4320-4327.
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