LFA-1 Ligation by High-Density ICAM-1 Is Sufficient To Activate IFN-γ Release by Innate T Lymphocytes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Akshat SharmaJenny E Gumperz

Abstract

By binding to its ligand ICAM-1, LFA-1 is known to mediate both adhesion and costimulatory signaling for T cell activation. The constitutively high LFA-1 cell surface expression of invariant NKT (iNKT) cells has been shown to be responsible for their distinctive tissue homing and residency within ICAM-rich endothelial vessels. However, the functional impact of LFA-1 on the activation of iNKT cells and other innate T lymphocyte subsets has remained largely unexplored. In particular, it is not clear whether LFA-1 contributes to innate-like pathways of T cell activation, such as IFN-γ secretion in response to IL-12. Using a recombinant ICAM-1-Fc fusion protein to stimulate human iNKT cells in the absence of APCs, we show that LFA-1 engagement enhances their IL-12-driven IFN-γ production. Surprisingly, exposure to high densities of ICAM-1 was also sufficient to activate iNKT cell cytokine secretion independently of IL-12 and associated JAK/STAT signaling. LFA-1 engagement induced elevated cytoplasmic Ca2+ and rapid ERK phosphorylation in iNKT cells, and the resulting IFN-γ secretion was dependent on both of these pathways. Analysis of freshly isolated human PBMC samples revealed that a fraction of lymphocytes that showed elevated L...Continue Reading

References

May 12, 1995·Science·A BendelacR R Brutkiewicz
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·S B KannerN K Damle
Jul 6, 2000·Immunopharmacology·S Matsuda, S Koyasu
Mar 22, 2002·Nature Reviews. Immunology·A BendelacJ F Kearney
Jul 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stéphane SidobreMitchell Kronenberg
Oct 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nadine Y CroweDale I Godfrey
Oct 28, 2003·Nature Immunology·Manfred BriglMichael B Brenner
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·John R OrtaldoRobert H Wiltrout
Apr 29, 2004·Blood·Yukihito NakaiKazunori Onoé
Oct 8, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Goichi MatsumotoJosef M Penninger
Dec 14, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Ara M AslanianIsrael F Charo
Jun 2, 2005·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Yuri V Bobryshev, Reginald S A Lord
Jan 31, 2006·Nature Immunology·Morgan HuseMark M Davis
Mar 7, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Manfred BriglJenny E Gumperz
Feb 22, 2007·Journal of Leukocyte Biology·Subramanya HegdeJenny E Gumperz
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Niranjana A Nagarajan, Mitchell Kronenberg
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiuxu ChenJenny E Gumperz
Jul 13, 2007·Immunological Reviews·Andrew SmithNancy Hogg
Aug 30, 2007·Journal of Leukocyte Biology·Xiuxu ChenJenny E Gumperz
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter VelázquezMichael L Dustin
Apr 15, 2008·Immunobiology·Susann BeetzDieter Kabelitz
Sep 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aaron J TyznikMitchell Kronenberg
Feb 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Carole GuillonneauStephen J Turner
Oct 28, 2009·PLoS Biology·Lisa M FoxJenny E Gumperz
Dec 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric S AlonzoDerek B Sant'Angelo
Nov 10, 2010·European Journal of Immunology·Emmanouil KyriakakisGennaro De Libero
Jan 25, 2011·Current Opinion in Immunology·Eric S Alonzo, Derek B Sant'Angelo
Apr 5, 2011·Trends in Immunology·Lionel Le BourhisOlivier Lantz
Jun 1, 2011·The Journal of Experimental Medicine·Seddon Y ThomasAlbert Bendelac
Aug 2, 2011·Nature Immunology·Daniel G PellicciJamie Rossjohn

❮ Previous
Next ❯

Citations

Nov 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Melissa BedardVincenzo Cerundolo
Jun 12, 2021·Life Science Alliance·Nicholas J HessJenny E Gumperz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.