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Infectious Th1 and Th2 autoimmunity in diabetes‐prone mice
Author(s) -
Tian Jide,
Olcott Angelica P,
Hanssen Lorraine R.,
Zekzer Dan,
Middleton Blake,
Kaufman Daniel L
Publication year - 1998
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1998.tb01214.x
Subject(s) - insulitis , autoimmunity , immunology , biology , beta cell , antigen , nod , autoimmune disease , beta (programming language) , immunopathology , t cell , disease , type 1 diabetes , antibody , immune system , medicine , diabetes mellitus , endocrinology , islet , computer science , programming language
Summary: In the non‐obese diabetic (NOD) mouse, a Thl‐biased autoimmune response arises spontaneously against glutamic acid decarboxylase, concurrent with the onset of insulitis. Subsequently, Th1‐type autore‐activity spreads intra‐ and intermolecularly to other β‐cell autoantigens (βCAAs), suggesting that a spontaneous Th1 cascade underlies disease progression. Induction of Th2 immunity to a single βCAA results in the spreading of Th2–type T‐cell and humoral responses to other βCAAs in an infectious manner. Thus, both Th1 and Th2 autoimmunity can evolve in amplificatory cascades defined by site‐specific, but not antigen‐specific, positive feedback circuits. Despite the continued presence of Th1 auto‐immunity, the induction of Th2 spreading is associated with active tolerance to βCAAs and reduced disease incidence. With disease progression there is an attenuation of βCAA‐inducible Th2 spreading, presumably because of a reduced availability of uncommitted βCAA‐reactive precursor T cells. We discuss the implications of these findings for the rational design of antigen‐based immunotherapeutics.