| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 149, Issue 9 3097-3106, Copyright © 1992 by American Association of Immunologists
ARTICLES |
T Giese and WF Davidson
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Mice homozygous for lpr and gld develop profound lymphadenopathy characterized by the accumulation of two functionally anergic T cell subsets, a predominant B220+CD4-CD8- double negative (DN) population and a minor, closely related CD4 dull+ B220+ population. Lymph nodes from diseased lpr and gld mice also contain abnormally high numbers of conventional T cells, and we reported recently that a high proportion of lpr and gld CD4+B220- T cells have the hallmarks of primed or memory T cells. In the present study, we further investigated the extent, ontogeny, and possible causes of T cell activation in lpr and gld mice. The criteria used to identify primed or memory T cells included activation-dependent increases in the expression of CD44, LFA-1, and the early activation Ag, CD69, and decreases in the expression of Mel- 14 and CD45RB, as well as quantitative differences in the in vitro production of IFN-gamma and the TNF-alpha by stimulated cells. A comparison of TCR V beta gene utilization by lpr T cell subsets also was undertaken. The results showed that T cell activation was widespread and complex. CD8+ T cells exhibited a similar pattern of activation to CD4+B220- T cells. The activation of these two subsets occurred in parallel, was in evidence by 4 to 6 wk of age, and was both chronic and progressive. The proportions of CD44hiLFA-1hi, CD4+B220-, and CD8+ T cells increased steadily between 4 and 20 wk of age, but changes in T cell growth, Mel-14, and CD45RB expression and cytokine secretion were not observed until mice were older than 11 wk. A very different pattern of activation was observed for B220+ T cells. At all ages, B220+ DN and CD4+B220+ T cells were CD44hiMel-14hi and 60 to 75% were CD69+. The expression of CD69 appeared to be stimulus dependent rather than constitutive, suggesting that these cells, too, may be chronically stimulated in vivo. In keeping with their anergic state, DN T cells responded poorly to cross-linking of CD69. The stimuli inducing chronic activation of CD4+B220- and CD8+ T cells are unlikely to include inappropriate reactions to autoantigens because there was no evidence for selective accumulation of CD4+ or CD8+ T cells bearing particular V beta genes or potentially self-reactive cells that normally are deleted in the thymus. By comparison, C3H-lpr DN cells displayed some potentially significant differences in V beta 6 and V beta 9 expression from CD4+B220- and CD8+ T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
This article has been cited by other articles:
|
|
 |
|
  M.-L. Yang, H. A. Doyle, R. J. Gee, J. D. Lowenson, S. Clarke, B. R. Lawson, D. W. Aswad, and M. J. Mamula Intracellular Protein Modification Associated with Altered T Cell Functions in Autoimmunity J. Immunol., October 1, 2006; 177(7): 4541 - 4549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. A. Hamad, A. S. Mohamood, C. J. Trujillo, C.-T. Huang, E. Yuan, and J. P. Schneck B220+ Double-Negative T Cells Suppress Polyclonal T Cell Activation by a Fas-Independent Mechanism That Involves Inhibition of IL-2 Production J. Immunol., September 1, 2003; 171(5): 2421 - 2426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Catterall, D. Stockwell, V. Marshall, A. Strasser, and J. Allison Autoimmune kidney disease and lymphadenopathy in NODlpr mice are not modified by deficiency in tumor necrosis factor receptor 1 or {beta}2-microglobulin Int. Immunol., June 1, 2003; 15(6): 679 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Davidson, C. Haudenschild, J. Kwon, and M. S. Williams T Cell Receptor Ligation Triggers Novel Nonapoptotic Cell Death Pathways That Are Fas-Independent or Fas-Dependent J. Immunol., December 1, 2002; 169(11): 6218 - 6230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Trimble, K. A. Prince, G. A. Pestano, J. Daley, and H. Cantor Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease J. Immunol., May 15, 2002; 168(10): 4960 - 4967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Wellmann, M. Letz, A. Schneider, K. Amann, and T. H. Winkler An Ig {micro}-heavy chain transgene inhibits systemic lupus erythematosus immunopathology in autoimmune (NZB x NZW)F1 mice Int. Immunol., December 1, 2001; 13(12): 1461 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Monneaux, H. Dumortier, G. Steiner, J.-P. Briand, and S. Muller Murine models of systemic lupus erythematosus: B and T cell responses to spliceosomal ribonucleoproteins in MRL/Faslpr and (NZB NZW)F1 lupus mice Int. Immunol., September 1, 2001; 13(9): 1155 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Fields, C. L. Sokol, A. Eaton-Bassiri, S.-j. Seo, M. P. Madaio, and J. Erikson Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells J. Immunol., August 15, 2001; 167(4): 2370 - 2378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. T. M. Chan and M. J. Shlomchik Cutting Edge: B Cells Promote CD8+ T Cell Activation in MRL-Faslpr Mice Independently of MHC Class I Antigen Presentation J. Immunol., February 15, 2000; 164(4): 1658 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schwarting, G. Tesch, K. Kinoshita, R. Maron, H. L. Weiner, and V. R. Kelley IL-12 Drives IFN-{gamma}-Dependent Autoimmune Kidney Disease in MRL-Faslpr Mice J. Immunol., December 15, 1999; 163(12): 6884 - 6891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. T. M. Chan, M. P. Madaio, and M. J. Shlomchik B Cells Are Required for Lupus Nephritis in the Polygenic, Fas-Intact MRL Model of Systemic Autoimmunity J. Immunol., October 1, 1999; 163(7): 3592 - 3596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mandik-Nayak, S.-j. Seo, C. Sokol, K. M. Potts, A. Bui, and J. Erikson MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti-double-stranded DNA B Cells J. Exp. Med., June 7, 1999; 189(11): 1799 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mohan, Y. Yu, L. Morel, P. Yang, and E. K. Wakeland Genetic Dissection of Sle Pathogenesis: Sle3 on Murine Chromosome 7 Impacts T Cell Activation, Differentiation, and Cell Death J. Immunol., June 1, 1999; 162(11): 6492 - 6502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. T.M. Chan, L. G. Hannum, A. M. Haberman, M. P. Madaio, and M. J. Shlomchik A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus J. Exp. Med., May 17, 1999; 189(10): 1639 - 1648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Mittelstadt and J. D. Ashwell Role of Egr-2 in Up-regulation of Fas Ligand in Normal T Cells and Aberrant Double-negative lpr and gld T Cells J. Biol. Chem., January 29, 1999; 274(5): 3222 - 3227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Davidson, T. Giese, and T. N. Fredrickson Spontaneous Development of Plasmacytoid Tumors in Mice with Defective Fas-Fas Ligand Interactions J. Exp. Med., June 1, 1998; 187(11): 1825 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kishimoto, C. D. Surh, and J. Sprent A Role for Fas in Negative Selection of Thymocytes In Vivo J. Exp. Med., May 4, 1998; 187(9): 1427 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fukuyama, M. Adachi, S. Suematsu, K. Miwa, T. Suda, N. Yoshida, and S. Nagata Transgenic Expression of Fas in T Cells Blocks Lymphoproliferation But Not Autoimmune Disease in MRL-lpr Mice J. Immunol., April 15, 1998; 160(8): 3805 - 3811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Chan and M. J. Shlomchik A New Role for B Cells in Systemic Autoimmunity: B Cells Promote Spontaneous T Cell Activation in MRL-lpr/lpr Mice J. Immunol., January 1, 1998; 160(1): 51 - 59. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
