| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Section of Clinical Immunology and Infectious Diseases and Research Institute for Internal Medicine, Medical Department A, Rikshospitalet, Oslo, Norway; and
Institute of Medical Biochemistry, University of Oslo, Oslo, Norway
The molecular mechanisms underlying the T cell dysfunction often present in common variable immunodeficiency (CVI) are not established. cAMP-dependent protein kinase A type I (PKAI) is an important inhibitor of T cell proliferation after Ag stimulation. We therefore investigated the possibility that activation of PKAI may be involved in the development of T cell dysfunction in CVI. An exogenously added PKAI-selective antagonist (Rp-8-Br-cAMPS) induced a significant increase in anti-CD3-stimulated PBMC proliferation in 20 CVI patients compared with no effect in 15 controls. Purified T cells from 7 CVI patients with strictly defined T cell deficiency had elevated endogenous cAMP levels compared with controls. Treatment of T cells from these CVI patients with Rp-8-bromo-cAMP-phosphorothioate markedly improved anti-CD3-stimulated proliferation (up to 3.7-fold), particularly in CD4+ lymphocytes, reaching proliferation levels comparable to control values. No effect of cAMP antagonist on T cell proliferation was seen in controls. In these CVI patients, cAMP antagonist also increased IL-2 production in anti-CD3-stimulated T cells. However, exogenously added IL-2 at concentrations comparable to the achieved increase in IL-2 levels after addition of cAMP antagonist had no effect on T cell proliferation. Furthermore, the stimulatory effects of exogenously added IL-2 at higher concentrations and cAMP antagonist on T cell proliferation were additive. Our findings indicate that increased PKAI activation may be an important molecular basis for the T cell defect in CVI and suggest that the cAMP/PKAI system may be a potential molecular target for immunomodulating therapy in these patients.
This article has been cited by other articles:
|
|
 |
|
  V. Bjerkeli, J. K. Damas, B. Fevang, J. C. Holter, P. Aukrust, and S. S. Froland Increased expression of fractalkine (CX3CL1) and its receptor, CX3CR1, in Wegener's granulomatosis possible role in vascular inflammation Rheumatology, September 1, 2007; 46(9): 1422 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Bryn, M. Mahic, J. M. Enserink, F. Schwede, E. M. Aandahl, and K. Tasken The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages. J. Immunol., June 15, 2006; 176(12): 7361 - 7370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Sandberg, A. Yndestad, E. Oie, C. Smith, T. Ueland, O. Ovchinnikova, A.-K. L. Robertson, F. Muller, A. G. Semb, H. Scholz, et al. Enhanced T-Cell Expression of RANK Ligand in Acute Coronary Syndrome: Possible Role in Plaque Destabilization Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 857 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Holven, J. K. Damas, A. Yndestad, T. Waehre, T. Ueland, B. Halvorsen, L. Heggelund, W. J. Sandberg, A. G. Semb, S. S. Froland, et al. Chemokines in Children With Heterozygous Familiar Hypercholesterolemia: Selective Upregulation of RANTES Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 200 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Damas, A. Boullier, T. Waehre, C. Smith, W. J. Sandberg, S. Green, P. Aukrust, and O. Quehenberger Expression of Fractalkine (CX3CL1) and its Receptor, CX3CR1, Is Elevated in Coronary Artery Disease and Is Reduced During Statin Therapy Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2567 - 2572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ueland, A. Yndestad, E. Oie, G. Florholmen, B. Halvorsen, S. S. Froland, S. Simonsen, G. Christensen, L. Gullestad, and P. Aukrust Dysregulated Osteoprotegerin/RANK Ligand/RANK Axis in Clinical and Experimental Heart Failure Circulation, May 17, 2005; 111(19): 2461 - 2468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-A. Amella, B. Sherry, D. H. Shepp, and H. Schmidtmayerova Macrophage Inflammatory Protein 1{alpha} Inhibits Postentry Steps of Human Immunodeficiency Virus Type 1 Infection via Suppression of Intracellular Cyclic AMP J. Virol., May 1, 2005; 79(9): 5625 - 5631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yndestad, T. Ueland, E. Oie, G. Florholmen, B. Halvorsen, H. Attramadal, S. Simonsen, S. S. Froland, L. Gullestad, G. Christensen, et al. Elevated Levels of Activin A in Heart Failure: Potential Role in Myocardial Remodeling Circulation, March 23, 2004; 109(11): 1379 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. TASKEN and E. M. AANDAHL Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A Physiol Rev, January 1, 2004; 84(1): 137 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yndestad, A. M Holm, F. Muller, S. Simonsen, S. S Froland, L. Gullestad, and P. Aukrust Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure Cardiovasc Res, October 15, 2003; 60(1): 141 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Holm, P. Aukrust, E. M. Aandahl, F. Muller, K. Tasken, and S. S. Froland Impaired Secretion of IL-10 by T Cells from Patients with Common Variable Immunodeficiency-Involvement of Protein Kinase A Type I J. Immunol., June 1, 2003; 170(11): 5772 - 5777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Johansson, M. K. Dahle, S. R. Blomqvist, L. M. Gronning, E. M. Aandahl, S. Enerback, and K. Tasken A Winged Helix Forkhead (FOXD2) Tunes Sensitivity to cAMP in T Lymphocytes through Regulation of cAMP-dependent Protein Kinase RIalpha J. Biol. Chem., May 2, 2003; 278(19): 17573 - 17579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Grader-Beck, A. A. F. L. van Puijenbroek, L. M. Nadler, and V. A. Boussiotis cAMP inhibits both Ras and Rap1 activation in primary human T lymphocytes, but only Ras inhibition correlates with blockade of cell cycle progression Blood, February 1, 2003; 101(3): 998 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vang, K. M. Torgersen, V. Sundvold, M. Saxena, F. O. Levy, B. S. Skalhegg, V. Hansson, T. Mustelin, and K. Tasken Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor J. Exp. Med., February 20, 2001; 193(4): 497 - 508. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
