The Journal of Immunology, Vol 151, Issue 1 119-127, Copyright © 1993 by American Association of Immunologists

ARTICLES

Suppressive effect of T cell proliferation via the CD29 molecule. The CD29 mAb 1 "K20" decreases diacylglycerol and phosphatidic acid levels in activated T cells

M Ticchioni, C Aussel, JP Breittmayer, S Manie, C Pelassy and A Bernard
Institut National de la Sante et de la Recherche Medicale INSERM U343, Nice, France.

We had previously reported that the CD29 mAb "K20," presented in a soluble form, blocks peripheral T cell proliferation/activation induced by a CD3 mAb. To better characterize the negative signal delivered by soluble K20, we have investigated its effects on the phospholipid metabolism, both in Jurkat and CD4+ T cells. In CD3-activated T cells, K20 inhibited the increase of diacylglycerol (DAG) and phosphatidic acid levels, but did not modify phosphatidylinositol 4,5-bisphosphate levels, cytosolic Ca2+ raise, and inositolphosphates formation, indicating that K20 did not inhibit phosphatidylinositol 4,5- bisphosphate hydrolysis by phospholipase C-gamma. Moreover, in these conditions, K20 increased phosphatidylethanolamine levels, without variation of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol, suggesting that K20 specifically increased the phosphatidylethanolamine biosynthesis from DAG. Thus, the effects of K20 on DAG and phosphatidic acid levels resulted from an accelerated catabolism rather than from a defect of synthesis. That K20 acts solely at an early step of T cell activation, namely before the binding of IL- 2 to its receptor, is supported by the observation that adding exogenous rIL-2 increased proliferation in spite of K20. These results suggest that the beta 1 integrin molecules interact with the membrane phospholipid metabolism and they appear to be the hallmark of a peculiar negative pathway of T cell activation, likely to play an important regulatory role mediated via the T cell integrin molecules.

This article has been cited by other articles:

				M. A. Rosenthal-Allieri, M. Ticchioni, J. P. Breittmayer, Y. Shimizu, and A. Bernard Influence of {beta}1 Integrin Intracytoplasmic Domains in the Regulation of VLA-4-Mediated Adhesion of Human T Cells to VCAM-1 under Flow Conditions J. Immunol., July 15, 2005; 175(2): 1214 - 1223. [Abstract] [Full Text] [PDF]

				A. Molla and M. R. Block Adherence of Human Erythroleukemia Cells Inhibits Proliferation without Inducing Differentiation Cell Growth Differ., February 1, 2000; 11(2): 83 - 90. [Abstract] [Full Text]

				M. Milella, A. Gismondi, P. Roncaioli, G. Palmieri, S. Morrone, M. Piccoli, L. Frati, M. G. Cifone, and A. Santoni {beta}1 Integrin Cross-Linking Inhibits CD16-Induced Phospholipase D and Secretory Phospholipase A2 Activity and Granule Exocytosis in Human NK cells: Role of Phospholipase D in CD16-Triggered Degranulation J. Immunol., February 15, 1999; 162(4): 2064 - 2072. [Abstract] [Full Text] [PDF]

				M. Vivinus-Nebot, M. Ticchioni, F. Mary, P. Hofman, V. Quaranta, P. Rousselle, and A. Bernard Laminin 5 in the Human Thymus: Control of T Cell Proliferation via alpha 6beta 4 Integrins J. Cell Biol., February 8, 1999; 144(3): 563 - 574. [Abstract] [Full Text] [PDF]

				S. Bechoua, M. Dubois, G. Némoz, M. Lagarde, and A.-F. Prigent Docosahexaenoic acid lowers phosphatidate level in human activated lymphocytes despite phospholipase D activation J. Lipid Res., April 1, 1998; 39(4): 873 - 883. [Abstract] [Full Text]

				R. J. Faull, J. Wang, D. I. Leavesley, W. Puzon, G. R. Russ, D. Vestweber, and Y. Takada A Novel Activating Anti-beta 1 Integrin Monoclonal Antibody Binds to the Cysteine-rich Repeats in the beta 1 Chain J. Biol. Chem., October 11, 1996; 271(41): 25099 - 25106. [Abstract] [Full Text] [PDF]