C. Atlangepner et al., DIFFERENT TH2-TH1 BALANCE IN V-BETA-8 AND V-BETA-6 SUBSETS OF SPLENOCYTES IN NOD FEMALES IN THE EARLY PHASE OF DIABETOGENESIS, Diabetes & metabolism, 23(5), 1997, pp. 386-394
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.