Early defect of immunoregulatory T cells in autoimmune diabetes.
A potential immunoregulatory function has recently been attributed to the discrete subset of major histocompatibility complex (MHC) class I-restricted TCR-alpha beta mature thymocytes expressing an unusual V beta 8-biased T cell receptor repertoire. This T cell subset which also selectively express the CD44 marker is the main IL-4 producer in the thymus. Nonobese diabetic (NOD) mice were found to have a marked deficit in the number and functional capacity of CD44+ TCR-alpha beta+ thymocytes from as early as 3 weeks of age. The deficiency in IL-4 production was completely corrected after incubation with interleukin-7 (IL-7), a selective growth factor for CD44+ TCR-alpha beta+ mature thymocytes. This abnormality in T cell differentiation could explain the Th2 functional deficiency that may be a key element in the emergence of Th1-driven autoimmune disease in NOD mice.
Gombert
J M
JM
INSERM U.25, hôpital Necker, Paris, France.
Herbelin
A
A
Tancrède-Bohin
E
E
Dy
M
M
Chatenoud
L
L
Carnaud
C
C
Bach
J F
JF
D000818:Animals; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D018960:Hyaluronan Receptors; D015851:Interleukin-7; D015847:Interleukin-4