The Journal of Immunology, Vol 146, Issue 12 4209-4214, Copyright © 1991 by American Association of Immunologists

ARTICLES

IL-4 inhibits IL-2 synthesis and IL-2-induced up-regulation of IL-2R alpha but not IL-2R beta chain in CD4+ human T cells

A Gaya, O de la Calle, J Yague, E Alsinet, MD Fernandez, M Romero, V Fabregat, J Martorell and J Vives
Servei d'Immunologia, Hospital Clinic, Barcelona, Spain.

There is growing evidence to suggest a regulatory role of IL-4 in the immune system affecting both proliferation and lymphokine production. In the present work we have analyzed the effect of IL-4 on IL-2 and IFN- gamma synthesis by stimulating CD4+ human T cells (+10% accessory cells) with Con A in the presence of several doses (1 to 100 U/ml) of human rIL-4. The results showed an impaired IL-2 and IFN-gamma synthesis in the presence of IL-4. This inhibition was dose dependent and was evident only when IL-4 was added in the first 2 h of culture. Moreover, the external addition of IL-2 did not revert the inhibitory effect of IL-4 on IL-2 and IFN-gamma synthesis induced by Con A. We have also analyzed the effect of IL-4 on the expression of both alpha- and beta-chains of the IL-2R. Although the expression of IL-2R alpha mRNA was not modified after 6 h in culture in the presence of IL-4, a decrease was observed at 24 and 48 h. The addition of rIL-2 showed that the inhibition in IL-2R alpha expression could be explained by an impairment in the up-regulatory signal transmitted through the IL-2R. In addition to this, IL-4 did not modify the IL-2R beta mRNA expression at 6 and 24 h although a decreased expression was observed at 48 h which could be explained by the defective IL-2 production. The differential effect of IL-4 on the up-regulatory effect of IL-2 in the expression of IL-2R alpha and IL-2R beta suggest the existence of different regulatory mechanisms acting on the expression of both chains.

This article has been cited by other articles:

				J. Zhang, T. Bardos, Q. Shao, J. Tschopp, K. Mikecz, T. T. Glant, and A. Finnegan IL-4 Potentiates Activated T Cell Apoptosis Via an IL-2-Dependent Mechanism J. Immunol., April 1, 2003; 170(7): 3495 - 3503. [Abstract] [Full Text] [PDF]

				M. A. De Francesco, M. Baronio, S. Fiorentini, C. Signorini, C. Bonfanti, C. Poiesi, M. Popovic, M. Grassi, E. Garrafa, L. Bozzo, et al. HIV-1 matrix protein p17 increases the production of proinflammatory cytokines and counteracts IL-4 activity by binding to a cellular receptor PNAS, July 23, 2002; 99(15): 9972 - 9977. [Abstract] [Full Text] [PDF]

				X. Y. Yang, L. H. Wang, K. Mihalic, W. Xiao, T. Chen, P. Li, L. M. Wahl, and W. L. Farrar Interleukin (IL)-4 Indirectly Suppresses IL-2 Production by Human T Lymphocytes via Peroxisome Proliferator-activated Receptor gamma Activated by Macrophage-derived 12/15-Lipoxygenase Ligands J. Biol. Chem., February 1, 2002; 277(6): 3973 - 3978. [Abstract] [Full Text] [PDF]

				M. J. Cuadrado, M. Marubayashi, C. Ortega, N. Fernandez-Arcas, F. Garcia-Cozar, J. Pena, P. Sanchez-Guijo, and M. Santamaria Relationship of IL-2, IL-2R (CD25+), Soluble IL-2R and IL-4 with Disease Activity in SLE Patients Lupus, August 1, 1993; 2(4): 257 - 260. [Abstract] [PDF]

				M. J. Cuadrado, M. Marubayashi, C. Ortega, N. Fernandez-Arcas, F. Garcia-Cozar, J. Pena, P. Sanchez-Guijo, and M. Santamaria Relationship of IL-2, IL-2R (CD25+), Soluble IL-2R and IL-4 with Disease Activity in SLE Patients Lupus, January 1, 1993; 2(1_suppl): 257 - 260. [Abstract] [PDF]