The Journal of Immunology, Vol 149, Issue 7 2513-2517, Copyright © 1992 by American Association of Immunologists

ARTICLES

Accelerated programmed cell death of MRL-lpr/lpr T lymphocytes

N Van Houten and RC Budd
Department of Medicine, University of Vermont, Burlington 05405.

MRL-lpr/lpr (lpr) mice develop a polyclonal accumulation of abnormal peripheral T lymphocytes, which bear surface alpha beta TCR, CD3, and the B220 isoform of CD45, but lack CD4, CD8, and CD2. These T cells have a constitutively phosphorylated CD3 zeta chain and manifest a defect in signal transduction that results in a lack of IL-2 production and proliferation. We investigated whether this signaling abnormality might contribute to their accumulation via a defect in T cell elimination in the periphery. T cell deletion occurs through a process of programmed cell death with DNA degradation, or apoptosis. Viable lymphocytes from lpr mice were found to undergo rapid programmed cell death in culture within 4 h without additional activation, which was not observed in lymphocytes from normal MRL-+/+ or C57BL/6-+/+ mice. Both nonmature B220+ and mature B220- T lymphocytes from lpr mice display this accelerated programmed cell death, indicating that this is a defect affecting all peripheral T lymphocytes in lpr mice. In vitro apoptosis of lpr T cells could be inhibited with PMA, a stimulator of protein kinase C. Thus, the massive accumulation of T lymphocytes in the lymphoid tissue of lpr mice is not due to a defect in their ability to undergo programmed cell death in vitro. The activation state of lpr T cells may contribute to their rapid degradation of DNA in vitro.

This article has been cited by other articles:

				S. Sengupta, P. Jayaraman, P. M. Chilton, C. R. Casella, and T. C. Mitchell Unrestrained Glycogen Synthase Kinase-3beta Activity Leads to Activated T Cell Death and Can Be Inhibited by Natural Adjuvant J. Immunol., May 15, 2007; 178(10): 6083 - 6091. [Abstract] [Full Text] [PDF]

				Y. Do, A. Q. Rafi-Janajreh, R. J. Mckallip, P. S. Nagarkatti, and M. Nagarkatti Combined deficiency in CD44 and Fas leads to exacerbation of lymphoproliferative and autoimmune disease Int. Immunol., November 1, 2003; 15(11): 1327 - 1340. [Abstract] [Full Text] [PDF]

				P. K. Potter, J. Cortes-Hernandez, P. Quartier, M. Botto, and M. J. Walport Lupus-Prone Mice Have an Abnormal Response to Thioglycolate and an Impaired Clearance of Apoptotic Cells J. Immunol., March 15, 2003; 170(6): 3223 - 3232. [Abstract] [Full Text] [PDF]

				J. Wang, X. Fan, C. Lindholm, M. Bennett, J. O'Connoll, F. Shanahan, E. G. Brooks, V. E. Reyes, and P. B. Ernst Helicobacter pylori Modulates Lymphoepithelial Cell Interactions Leading to Epithelial Cell Damage through Fas/Fas Ligand Interactions Infect. Immun., July 1, 2000; 68(7): 4303 - 4311. [Abstract] [Full Text] [PDF]

				M. L. Stoll and J. Gavalchin Systemic lupus erythematosus--messages from experimental models Rheumatology, January 1, 2000; 39(1): 18 - 27. [Full Text] [PDF]

				C. Odaka and T. Mizuochi Role of Macrophage Lysosomal Enzymes in the Degradation of Nucleosomes of Apoptotic Cells J. Immunol., November 15, 1999; 163(10): 5346 - 5352. [Abstract] [Full Text] [PDF]

				P. F. Mixter, J. Q. Russell, G. J. Morrissette, C. Charland, D. Aleman-Hoey, and R. C. Budd A Model for the Origin of TCR-{alpha}{beta}+ CD4-CD8- B220+ Cells Based on High Affinity TCR Signals J. Immunol., May 15, 1999; 162(10): 5747 - 5756. [Abstract] [Full Text] [PDF]

				T Papo, C Parizot, M Ortova, J-C Piette, C Frances, P Debre, P Godeau, and G Gorochov Apoptosis and expression of soluble Fas mRNA in systemic lupus erythematosus Lupus, September 1, 1998; 7(7): 455 - 461. [Abstract] [PDF]

				X. Fan, S. E. Crowe, S. Behar, H. Gunasena, G. Ye, H. Haeberle, N. Van Houten, W. K. Gourley, P. B. Ernst, and V. E. Reyes The Effect of Class II Major Histocompatibility Complex Expression on Adherence of Helicobacter pylori and Induction of Apoptosis in Gastric Epithelial Cells: A Mechanism for T Helper Cell Type 1-mediated Damage J. Exp. Med., May 18, 1998; 187(10): 1659 - 1669. [Abstract] [Full Text] [PDF]

				E.S. Sobel Cellular Interactions in the LPR and GLD Models of Systemic Autoimmunity Advances in Dental Research, April 1, 1996; 10(1): 76 - 80. [Abstract] [PDF]