DIRECT THYMIC INVOLVEMENT IN ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION - EVIDENCE FOR A NONDELETIONAL MECHANISM OF CENTRALLY INDUCED TOLERANCE TO EXTRATHYMIC ANTIGENS IN ADULT MICE
Yf. Wang et al., DIRECT THYMIC INVOLVEMENT IN ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION - EVIDENCE FOR A NONDELETIONAL MECHANISM OF CENTRALLY INDUCED TOLERANCE TO EXTRATHYMIC ANTIGENS IN ADULT MICE, The Journal of immunology, 158(5), 1997, pp. 2150-2155
Recent reports have suggested that the dichotomy between central (thym
ic) and peripheral T cell tolerance is not absolute and that self-tole
rance in perinatal animals may also involve the intrathymic generation
and release to the periphery of Ag-specific immunoregulatory T cells.
We have expanded this concept to include tolerance to non self Ags ad
ministered extrathymically to adult animals. In this study, we use the
anterior chamber-associated immune deviation (ACAID) to demonstrate t
hat central regulation of acquired peripheral tolerance can be induced
in adult mice by the intraocular administration of low doses of nonse
lf Ag. The results show that adult thymectomy prevents the inhibition
of trinitrophenol (TNP)-specific delayed-type hypersensitivity, which
normally occurs after injection of TNP-BSA into the anterior chamber (
AC) of the eye. Thymocytes obtained from mice 1 to 3 days, but not 5 t
o 7 days, after AC injection of TNP-BSA or BSA alone specifically tran
sfer inhibition of delayed-type hypersensitivity to mice primed with t
he homologous Ag. The latter observation, when correlated with the tim
e of onset of ACAID, suggests that immunoregulatory T cells are formed
in the thymus within 24 h and are exported to the peripheral lymphoid
tissues between 2 and 5 days after AC injection of Ag. Immunomagnetic
separation of thymocytes revealed that the immunoregulatory activity
resides within the minor subset of CD4(-), CD8(-), TCR-alpha beta(+) c
ells, previously postulated to induce fas ligand-mediated apoptosis an
d Th1 to Th2 immune deviation. Hence, the present study identifies ACA
ID as a prototypical model of centrally induced, nondeletional toleran
ce to extrathymic nonself Ags.