Intrathymic elimination of Mlsa-reactive (V beta 6+) cells during neonatal tolerance induction to Mlsa-encoded antigens.

• DOI: 10.1084/jem.167.6.2005
• Publication Date: 2004-06-24T07:56:10Z
• Authors: H R MacDonald; T Pedrazzini; R Schneider; J A Louis; R M Zinkernagel; H Hengartner
• Keywords: 0301 basic medicine; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; Receptors, Antigen, T-Cell; Thymus Gland; Minor Lymphocyte Stimulatory Antigens; 3. Good health; Mice; 03 medical and health sciences; Animals, Newborn; Antigens, Surface; Immune Tolerance; Animals; Antigens, Ly; Lymph Nodes

The cellular basis of neonatally induced T cell tolerance has been investigated in a model system in which usage of a particular TCR V beta segment (V beta 6) is strongly correlated with reactivity to antigens encoded by the Mlsa genetic locus. Expression of V beta 6 by peripheral T cells was virtually abolished in BALB/c (H-2d, Mlsb) mice rendered neonatally tolerant to DBA/2 (H-2d, Mlsa) lymphoid cells, whereas control V beta 8-bearing T cells remained at near normal levels. Further analysis revealed that elimination of V beta 6+ T cells occurred in the thymus of neonatally tolerant mice and could not be explained by receptor modulation or T cell chimerism. These data thus support the clonal deletion model of tolerance induction.