INTERCELLULAR-ADHESION MOLECULE-1 AND LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 ARE INVOLVED IN PROTECTION MEDIATED BY CD3-ALPHA-BETA- T-CELLS AT THE EARLY-STAGE AFTER INFECTION WITH LISTERIA-MONOCYTOGENES IN RATS(TCR)

To investigate the significance of intercellular adhesion molecule-1 ( ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) in host de fense against infection with intracellular parasites, we examined the effects of in vivo pretreatment with mAbs to ICAM-1 (1A29) and LFA-1al pha (WT-1) on the protection against infection with Listeria monocytog enes in Fisher F344/N rats. Expression of ICAM-1 and LFA-1alpha molecu les on T cells in spleen, liver and peritoneal cavity of rats was down -regulated after i.p. administration with daily doses of 300 mug of ei ther 1A29 or WT-1 for 10 days. The survival rate of rats inoculated wi th viable Listeria was significantly reduced by in vivo pretreatment w ith 1A29 together with WT-1 for 10 days but not by in vivo pretreatmen t with control mAb. The numbers of bacteria in the spleen in rats pret reated with both 1A29 and WT-1 were significantly increased on day 3 a nd day 6 after infection with 1 x 10(7) of viable Listeria correspondi ng to 1/30 of LD50 to normal rats. Thus, the resistance against lister ial infection was severely impaired by combinational pretreatment with mAbs in ICAM-1 and LFA-1alpha. As shown in our previous report, the e arly appearance of CD3+TCRalphabeta- T cells, presumably TCR gammadelt a T cells, was evident in the peritoneal cavity and liver of control r ats at the early stage after listerial infection, while this was suppr essed at this stage in rats pretreated with both 1A29 and WT1. These r esults suggest that the ICAM-1 and LFA-1 adhesion pathway may be criti cally involved in protective roles of CD3+TCRalphabeta- T cells at the early stage of rat listeriosis.