PROPIONIBACTERIUM-ACNES TREATMENT DIMINISHES CD4(-CELLS BUT INDUCES TYPE-I T-CELLS IN THE LIVER BY INDUCTION OF IL-12 AND IL-18 PRODUCTION FROM KUPFFER-CELLS() NK1.1(+) T)

LPS injection into normal mice does not induce liver injury, while the same treatment of Propionibacterium acnes-primed mice induces severe liver injury, indicating that P. acnes treatment renders the mice susc eptible to LPS. Since IFN-gamma sensitizes macrophages to LPS, we inve stigated the mechanism of induction and activation of IFN-gamma-produc ing (type 1) T cells by P. acnes. Twenty percent of liver lymphocytes of C57BL/6 mice are CD4(+)NK1.1(+) T cells that promptly produce IL-4 in response to anti-CDS in vitro. However, P. acnes treatment diminish ed these lymphocytes. Therefore, liver lymphocytes from P. acnes-prime d mice showed reduced IL-4 production. Furthermore, P. acnes treatment induced CD4(-) type 1 T cells in the liver. Isolated P. acnes-elicite d Kupffer cells produced IL-12 and to a lesser degree IL-18 in vitro. Injection of anti-IL-12 Ab totally abrogated these actions of P. acnes , while injection of anti-IL-18 Ab caused only partial abrogation. Thu s, administration of P. acnes diminished CD4(+)NK1.1(+) T cells, but i nduced type 1 T cells in the liver by induction of IL-12 and IL-18 pro duction. Injection of IL-12 (similar to 1,000 ng) dose dependently dim inished CD4(+)NK1.1(+) T cells, but induced type 1 T cells. In contras t, injection of IL-18 (similar to 1,000 ng) failed, although injection of a much larger dose of IL-18 (10,000 ng) or IL-18 (similar to 1,000 ng) with suboptimal doses of IL-12 (1-100 ng) diminished CD4(+)NK1.1( +) T cells in a dose-dependent manner. Thus, P. acnes treatment render s the mice highly susceptible to LPS by induction and activation of ty pe 1 T cells.