ANTIBODIES AGAINST MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGENSDIRECTLY INHIBIT THE GROWTH OF T-CELLS INFECTED WITH THEILERIA-PARVA WITHOUT AFFECTING THEIR STATE OF ACTIVATION

We have analyzed the effect of antibodies (Abs) directed against major histocompatibility complex (MHC) class II Abs on the proliferation of Theileria parva-infected (Tpi) T cells. Anti-MHC class II Abs exert a direct effect on Tpi T cells causing an acute block in their prolifer ation. The inhibition does not involve apoptosis and is also entirely reversible. The rapid arrest of DNA synthesis caused by anti-MHC class II Abs is not due to interference with the state of activation of the T cells since the transcriptional activator NF-kappaB remains activat ed in arrested cells. In addition, interleukin 2 (IL-2), IL-2R, and c- myc gene expression are also unaffected. By analyzing the cell-cycle p hase distribution of inhibited cells, it could be shown that cells in all phases of the cell cycle are inhibited. The signal transduction pa thway that results in inhibition was shown to be independent of protei n kinase C and extracellular Ca2+. Tyrosine kinase inhibitors, however , partly reduced the level of inhibition and, conversely, phosphatase inhibitors enhanced it. The possible relevance of this phenomenon in o ther systems is discussed.