Cryptocrine signaling in the thymus network and T cell education to neuroendocrine self-antigens.
Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes.
Department of Medicine-Endocrinology, University of Liège, Liège-Sart Tilman, Belgium.
V
V
Geenen
B
B
Goxe
H
H
Martens
E
E
Vandersmissen
Y
Y
Vanneste
I
I
Achour
O
O
Kecha
P J
PJ
Lefebvre
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000276:immunology*; D012065:Relaxin / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D001324:Autoantigens; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012065:Relaxin