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 au toimmune 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 th ese 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 subs ets 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 mi ce. No significant bias in T-cell receptor usage was noted in the sple en of these animals, whereas V beta 6+ lymphocytes could he very effic iently stimulated by interleukin-4 and also produce low but delectable 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 c ells to respond to or secrete interleukin-2 and interleukin-4, indicat ing a functional imbalance of the T-cell repertoire expanded by the au toimmune process.