Different TH2-TH1 balance in V beta 8 and V beta 6 subsets of splenocytes in NOD females in the early phase of diabetogenesis.
Non-obese diabetic (NOD) mice spontaneously develop T-cell-mediated autoimmune diabetes. Initial work on the diabetogenic T-cell repertoire indicated that autoreactive T lymphocytes were polyclonal but that the presence of specific subsets (V beta 8 or V beta 6) might be required for induction of the disease. Further functional analysis of NOD mice T lymphocytes was limited because of the relative anergic state of these cells due to abnormal patterns of cytokine secretion. The purpose of the present study was to establish experimental conditions allowing the exploration of the functional features of minor T-lymphocyte subsets in vitro using low doses of cofactors. The ability of splenocytes to proliferate, respond to, or secrete interleukin-2 and interleukin-4 was explored in young, pre-diabetic or old non-diabetic female NOD mice. No significant bias in T-cell receptor usage was noted in the spleen of these animals, whereas V beta 6 + lymphocytes could be very efficiently stimulated by interleukin-4 and also produce low but detectable amounts of interleukin-4 during the pre-diabetic period in female NOD mice. These results suggest that diabetes induction is preceded by V beta + subset-specific functional changes in the ability of various T cells to respond to or secrete interleukin-2 and interleukin-4, indicating a functional imbalance of the T-cell repertoire expanded by the autoimmune process.
Atlan-Gepner
C
C
Service d'Endocrinologie Nutrition et Maladies métaboliques, Hôpital Sainte Marguerite, Marseille, France.
Hermitte
L
L
Janand-Delenne
B
B
Naquet
P
P
Vialettes
B
B
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D013045:Species Specificity; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D017252:CD3 Complex; D007376:Interleukin-2; D015847:Interleukin-4