Different modes of pathogenesis in T-cell-dependent autoimmunity: clues from two TCR transgenic systems.
T lymphocytes constantly flirt with reactivity to self peptides, a price they pay for their ability to recognize foreign peptides presented by self-MHC molecules, and autoreactivity in the T compartment occasionally gives rise to autoimmune disease. Pathology from T-cell autoimmunity can manifest itself through radically different strategies, as we have observed recently in two transgenic models. In the BDC2.5 diabetes model, T cells express a transgene-encoded T-cell receptor (TCR) with reactivity against a pancreatic antigen. This leads to a massive, if often controlled, infiltration of the pancreatic islets. Target cell destruction then results from the local consequences of this local immune/inflammatory process. On the other hand, the arthritic manifestations of the KRN transgenic model are indirect: the transgenic TCR confers a broad autoreactivity, through which T cells stimulate B cells to produce arthritogenic immunoglobulins. These molecules are then sufficient to produce the disease, even in the complete absence of any lymphocytes. Although important questions subsist in this model--how the KRN T cells interfere with B-cell tolerance, what the target of arthritogenic IgG is--its implication is that an isolated T-cell dysregulation may manifest itself through an Ig-mediated disease.
Ji
H
H
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), Strasbourg, France.
Korganow
A S
AS
Mangialaio
S
S
Höglund
P
P
André
I
I
Lühder
F
F
Gonzalez
A
A
Poirot
L
L
Benoist
C
C
Mathis
D
D
D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell