SUPERANTIGEN-INDUCED ANERGY OF V-BETA-8(-CELLS INDUCES FUNCTIONAL BUTNONPROLIFERATIVE T-CELLS IN-VIVO() CD4(+) T)

The response profile of staphylococcal enterotoxin B (SEB)-primed muri ne V beta 8(+) CD4(+) and V beta 8(+) CD8(+) T cells was analysed upon rechallenge in vitro. While in vitro responses to secondary stimulati on with SEB were reduced to background levels, the in vivo reactivity after rechallenge with SEB was retained, in that SEB-primed mice succu mbed to lethal T-cell shock, lymphokines [interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma), tumour necrosis facto r-a (TNF-alpha)], and lymphokine-specific mRNA accumulation could be d etected in V beta 8(+) CD4(+) and V beta 8(+) CD8(+) T cells. However, V beta 8(+) CD4(+) T cells failed to enter the cell cycle. While the phenotype of V beta 8(+) CD8(+) T cells was indistinguishable from tha t of their counterparts from naive mice, V beta 8(+) CD4(+) T cells ex hibited in vivo an unusual phenotype as non-proliferative but function al T cells. We conclude that in vitro-defined anergy does not disclose the functional abilities of ligand-reactive V beta 8(+) T cells in vi vo, and that priming with superantigen (SAg) induces in vivo a differe ntiation of SEB-reactive V beta 8(+) CD4(+) T cells into a non-prolife rative but functional phenotype.