| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
The wide diversity of the T and B Ag receptor repertoires becomes even more extensive postneonatally due to the activity of TdT, which adds nontemplated N nucleotides to Ig and TCR coding ends during V(D)J recombination. In addition, complementarity-determining region 3 sequences formed in the absence of TdT are more uniform due to the use of short sequence homologies between the V, D, and J genes. Thus, the action of TdT produces an adult repertoire that is both different from, and much larger than, the repertoire of the neonate. We have generated TdT-deficient nonobese diabetic (NOD) and MRL-Faslpr mice, and observed a decrease in the incidence of autoimmune disease, including absence of diabetes and decreased pancreatic infiltration in NOD TdT-/- mice, and reduced glomerulonephritis and increased life span in MRL-Faslpr TdT-/- mice. Using tetramer staining, TdT-/- and TdT+/+ NOD mice showed similar frequencies of the diabetogenic BDC 2.5 CD4+ T cells. We found no increase in CD4+CD25+ regulatory T cells in NOD TdT-/- mice. Thus, TdT deficiency ameliorates the severity of disease in both lupus and diabetes, two very disparate autoimmune diseases that affect different organs, with damage conducted by different effector cell types. The neonatal repertoire appears to be deficient in autoreactive T and/or B cells with high enough affinities to induce end-stage disease. We suggest that the paucity of autoreactive specificities created in the N region-lacking repertoire, and the resultant protection afforded to the newborn, may be the reason that TdT expression is delayed in ontogeny.
This article has been cited by other articles:
|
|
 |
|
  J. B. Carey, C. S. Moffatt-Blue, L. C. Watson, A. L. Gavin, and A. J. Feeney Repertoire-based selection into the marginal zone compartment during B cell development J. Exp. Med., September 1, 2008; 205(9): 2043 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. M. Haeryfar, H. D. Hickman, K. R. Irvine, D. C. Tscharke, J. R. Bennink, and J. W. Yewdell Terminal Deoxynucleotidyl Transferase Establishes and Broadens Antiviral CD8+ T Cell Immunodominance Hierarchies J. Immunol., July 1, 2008; 181(1): 649 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kokeny, M. Godo, E. Nagy, M. Kardos, K. Kotsch, P. Casalis, C. Bodor, L. Rosivall, H-D. Volk, A.C. Zenclussen, et al. Skin disease is prevented but nephritis is accelerated by multiple pregnancies in autoimmune MRL/LPR mice Lupus, July 1, 2007; 16(7): 465 - 477. [Abstract] [PDF]
|
|
|
|
|
|
C. Jiang, J. Foley, N. Clayton, G. Kissling, M. Jokinen, R. Herbert, and M. Diaz Abrogation of Lupus Nephritis in Activation-Induced Deaminase-Deficient MRL/lpr Mice J. Immunol., June 1, 2007; 178(11): 7422 - 7431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fazilleau, C. Delarasse, I. Motta, S. Fillatreau, M.-L. Gougeon, P. Kourilsky, D. Pham-Dinh, and J. M. Kanellopoulos T Cell Repertoire Diversity Is Required for Relapses in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2007; 178(8): 4865 - 4875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Watson, C. S. Moffatt-Blue, R. Z. McDonald, E. Kompfner, D. Ait-Azzouzene, D. Nemazee, A. N. Theofilopoulos, D. H. Kono, and A. J. Feeney Paucity of V-D-D-J Rearrangements and VH Replacement Events in Lupus Prone and Nonautoimmune TdT-/- and TdT+/+ Mice J. Immunol., July 15, 2006; 177(2): 1120 - 1128. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
