Systemic treatment of anti-CD4CD25 T cell monoclonal antibody exacerbates sialoadenitis in submandibular glands during the early life in lupus-prone female NZB x NZWF mice.
BACKGROUND
The maintenance mechanisms of peripheral tolerance by CD4(+)CD25(+) T cells before the development of sialoadenitis in secondary Sjögren's syndrome (sSS) are not well understood. The aim of the present study is to examine the effect of reduction of CD4(+)CD25(+) T cells on the development of sialoadenitis during the early life in female NZB x NZWF(1) (B/WF(1)) mice, a model for human sSS.


METHODS
Female B/WF(1) mice at 3 days after birth were treated with either anti-mouse CD4(+)CD25(+) T cells rat IgG(1) monoclonal antibody (mAb) or Rat IgG(1)(control). At 25 weeks of age, autoantibodies against nucleus and cytoplasm of ductal epithelial and myoepithelial cells, and histpathology of submandibular glands were examined in the mAb-treated and control groups. Also the development of anti-Ro/SS-A antibodies was examined until 25 weeks of age in both groups.


RESULTS
The mAb-treated group showed severe lesions with the development of autoantibodies compared to the control group.


CONCLUSIONS
The present results suggest that peripheral CD4(+)CD25(+) T cells may, at least in part, contribute to down-regulate the development of sialoadenitis in submandibular glands of lupus-prone female B/WF(1) mice during their early life.
Hayashi
Toshiharu
T
Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, Yoshida, Yamaguchi, Japan. hayasi@yamaguchi-u.ac.jp
Adachi
Chie
C
Hasegawa
Keiko
K
D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains; D012793:Sialadenitis / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology; D013363:Submandibular Gland / Q000276:immunology / Q000473:pathology; D013364:Submandibular Gland Diseases / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D053645:Interleukin-2 Receptor alpha Subunit; C035356:SS-A antibodies