| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Program in Immunology and Virology and Program in Molecular Medicine, and
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655; and
Department of Pathology, University of Connecticut Health Center, Farmington, CT 06030
Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous
autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic
emigrants disappear rapidly from peripheral lymphoid tissues. DP-BB
rats are consequently lymphopenic and circulate severely reduced
numbers of T cells. Peripheral T cells present are phenotypically
immature (Thy1+) and appear activated. We
hypothesized that DP-BB recent thymic emigrants have a shortened life
span and disappear by apoptosis. The percentage of T cells with an
ßTCRlowB220+CD4-CD8-
phenotype was increased in DP peripheral lymphoid tissues when compared
with normal, nonlymphopenic diabetes-resistant (DR) BB rat tissues.
There was no evidence of DNA fragmentation in freshly isolated DP- or
DR-BB rat cells, but, after 24 h of culture, a higher proportion
of DP- than DR-BB splenic T cells underwent apoptosis. We then tested
the hypothesis that BB rat T cells with the
ßTCRlowB220+CD4-CD8-
phenotype accumulate and undergo apoptosis in the liver. Such cells
were observed undergoing apoptosis in both DP- and DR-BB rats, but
comprised 
80% of intrahepatic T cells in DP vs 20% in DR-BB
rats. Most
ßTCRlowB220+CD4-CD8-
cells in the liver were also Thy1+. The data suggest that T
cell apoptosis in the DP-BB rat is underway in peripheral lymphoid
tissues and is completed in the liver. Increased intrahepatic apoptosis
of recent thymic emigrants appears in part responsible for lymphopenia
in DP-BB rats and the concomitant predisposition of these animals to
autoimmunity.
This article has been cited by other articles:
|
|
 |
|
  J.-L. Hillebrands, B. Whalen, J. T. J. Visser, J. Koning, K. D. Bishop, J. Leif, J. Rozing, J. P. Mordes, D. L. Greiner, and A. A. Rossini A Regulatory CD4+ T Cell Subset in the BB Rat Model of Autoimmune Diabetes Expresses Neither CD25 Nor Foxp3 J. Immunol., December 1, 2006; 177(11): 7820 - 7832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schnell, C. Demolliere, P. van den Berk, and H. Jacobs Gimap4 accelerates T-cell death Blood, July 15, 2006; 108(2): 591 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Murray and I. N. Crispe TNF-{alpha} Controls Intrahepatic T Cell Apoptosis and Peripheral T Cell Numbers J. Immunol., August 15, 2004; 173(4): 2402 - 2409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Todd, E. M. Forsberg, D. L. Greiner, J. P. Mordes, A. A. Rossini, and R. Bortell Deficiencies in Gut NK Cell Number and Function Precede Diabetes Onset in BB Rats J. Immunol., May 1, 2004; 172(9): 5356 - 5362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Hosea, E. S. Rector, and C. G. Taylor Zinc-Deficient Rats Have Fewer Recent Thymic Emigrant (CD90+) T Lymphocytes in Spleen and Blood J. Nutr., December 1, 2003; 133(12): 4239 - 4242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pandarpurkar, L. Wilson-Fritch, S. Corvera, H. Markholst, L. Hornum, D. L. Greiner, J. P. Mordes, A. A. Rossini, and R. Bortell Ian4 is required for mitochondrial integrity and T cell survival PNAS, September 2, 2003; 100(18): 10382 - 10387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hornum, J. Romer, and H. Markholst The Diabetes-Prone BB Rat Carries a Frameshift Mutation in Ian4, a Positional Candidate of Iddm1 Diabetes, June 1, 2002; 51(6): 1972 - 1979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Todd, D. L. Greiner, A. A. Rossini, J. P. Mordes, and R. Bortell An Atypical Population of NK Cells That Spontaneously Secrete IFN-{gamma} and IL-4 Is Present in the Intraepithelial Lymphoid Compartment of the Rat J. Immunol., October 1, 2001; 167(7): 3600 - 3609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Z. Mehal, F. Azzaroli, and I. N. Crispe Antigen Presentation by Liver Cells Controls Intrahepatic T Cell Trapping, Whereas Bone Marrow-Derived Cells Preferentially Promote Intrahepatic T Cell Apoptosis J. Immunol., July 15, 2001; 167(2): 667 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dao, M. Exley, W. Z. Mehal, S. M. A. Tahir, S. Snapper, M. Taniguchi, S. P. Balk, and I. N. Crispe Involvement of CD1 in Peripheral Deletion of T Lymphocytes Is Independent of NK T Cells J. Immunol., March 1, 2001; 166(5): 3090 - 3097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Seung, N. Iwakoshi, B. A. Woda, T. G. Markees, J. P. Mordes, A. A. Rossini, and D. L. Greiner Allogeneic hematopoietic chimerism in mice treated with sublethal myeloablation and anti-CD154 antibody: absence of graft-versus-host disease, induction of skin allograft tolerance, and prevention of recurrent autoimmunity in islet-allografted NOD/Lt mice Blood, March 15, 2000; 95(6): 2175 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Z. Mehal, A. E. Juedes, and I. N. Crispe Selective Retention of Activated CD8+ T Cells by the Normal Liver J. Immunol., September 15, 1999; 163(6): 3202 - 3210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Y. Wu and I. Goldschneider Cyclosporin A-Induced Autologous Graft-Versus-Host Disease: A Prototypical Model of Autoimmunity and Active (Dominant) Tolerance Coordinately Induced by Recent Thymic Emigrants J. Immunol., June 1, 1999; 162(11): 6926 - 6933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ramanathan and P. Poussier T Cell Reconstitution of BB/W Rats After the Initiation of Insulitis Precipitates the Onset of Diabetes J. Immunol., May 1, 1999; 162(9): 5134 - 5142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Whalen, P. Weiser, J. Marounek, A. A. Rossini, J. P. Mordes, and D. L. Greiner Recapitulation of Normal and Abnormal BioBreeding Rat T Cell Development in Adult Thymus Organ Culture J. Immunol., April 1, 1999; 162(7): 4003 - 4012. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
