| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Departments of
*
Pathology and
Microbiology, University of Virginia, Charlottesville, VA 22908
Although human maternal autoantibodies may transfer transient manifestation of autoimmune disease to their progeny, some neonatal autoimmune diseases can progress, leading to the loss of tissue structure and function. In this study we document that murine maternal autoantibody transmitted to progeny can trigger de novo neonatal pathogenic autoreactive T cell response and T cell-mediated organ-specific autoimmune disease. Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice. Neonatal AOD did not occur in T cell-deficient pups, and the ovarian pathology was transferable by CD4+ T cells from diseased donors. Interestingly, neonatal AOD occurred only in pups exposed to ZP3 autoantibody from neonatal days 1–5, but not from day 7 or day 9. The disease susceptibility neonatal time window was not related to a propensity of neonatal ovaries to autoimmune inflammation, and it was not affected by infusion of functional adult CD4+CD25+ T cells. However, resistance to neonatal AOD in 9-day-old mice was abrogated by CD4+CD25+ T cell depletion. Finally, neonatal AOD was blocked by Ab to IgG-FcR, and interestingly, the disease was not elicited by autoantibody to a second, independent native ZP3 B cell epitope. Therefore, a new mechanism of neonatal autoimmunity is presented in which epitope-specific autoantibody stimulates de novo autoimmune pathogenic CD4+ T cell response.
This article has been cited by other articles:
|
|
 |
|
  I. Gavanescu, C. Benoist, and D. Mathis B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients PNAS, September 2, 2008; 105(35): 13009 - 13014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Maurel and C. Kanellopoulos-Langevin Heredity--Venturing Beyond Genetics Biol Reprod, July 1, 2008; 79(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. T. Samy, L. A. Parker, C. P. Sharp, and K. S.K. Tung Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node J. Exp. Med., September 19, 2005; 202(6): 771 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Goswami and G. S. Conway Premature ovarian failure Hum. Reprod. Update, July 1, 2005; 11(4): 391 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vernochet, S. M. Caucheteux, M.-C. Gendron, J. Wantyghem, and C. Kanellopoulos-Langevin Affinity-Dependent Alterations of Mouse B Cell Development by Noninherited Maternal Antigen Biol Reprod, February 1, 2005; 72(2): 460 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Y. Setiady, P. Pramoonjago, and K. S. K. Tung Requirements of NK Cells and Proinflammatory Cytokines in T Cell-Dependent Neonatal Autoimmune Ovarian Disease Triggered by Immune Complex J. Immunol., July 15, 2004; 173(2): 1051 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nemni, L. M. Caniatti, M. Gironi, E. Bazzigaluppi, and D. De Grandis Stiff person syndrome does not always occur with maternal passive transfer of GAD65 antibodies Neurology, June 8, 2004; 62(11): 2101 - 2102. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
