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.
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.
Ticchioni
M
M
Institut National de la Santé et de la Recherche Médicale INSERM U343, Nice, France.
Aussel
C
C
Breittmayer
J P
JP
Manié
S
S
Pelassy
C
C
Bernard
A
A
D015703:Antigens, CD / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D019012:Integrin beta1; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008563:Membrane Lipids / Q000276:immunology; D010712:Phosphatidic Acids / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000502:physiology; D015398:Signal Transduction
D015703:Antigens, CD; D017252:CD3 Complex; D004075:Diglycerides; D019012:Integrin beta1; D007376:Interleukin-2; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010714:Phosphatidylethanolamines; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D015375:Receptors, Interleukin-2; D016718:Arachidonic Acid; D000242:Cyclic AMP