UNRESPONSIVENESS TO 2,4-DINITRO-1-FLUORO-BENZENE AFTER TREATMENT WITHMONOCLONAL-ANTIBODIES TO LEUKOCYTE FUNCTION-ASSOCIATED MOLECULE-1 ANDINTERCELLULAR-ADHESION MOLECULE-1 DURING SENSITIZATION

We have investigated whether hapten-specific unresponsiveness could be induced if the interaction between LFA-1 (CD11a/CD18) and intercellul ar adhesion molecule-1 (CD54) was disrupted by blocking mAbs given to mice during sensitization with 2,4-dinitro-1-fluoro-benzene. An extend ed period of more than 11 days between the last i.p. injection of mAb and challenge was chosen to ensure that the mAb did not persist in the animals at the time of hapten challenge, as analyzed by flow cytometr y and immunohistochemistry. The contact sensitivity response was signi ficantly reduced (p < 0.001) when a combination of mAb FD441.8 against LFA-1 and mAb YNI/1.7.4 against intercellular adhesion molecule-1 was given during the sensitization phase compared with normal rat IgG-tre ated control animals, Furthermore, the animals were resistant to resen sitization to the same hapten, This hyporesponsiveness was hapten spec ific, since the contact sensitivity reaction of mAb-treated mice to ox azolone was the same as that of normal rat IgG-treated control animals , Together these data indicate that inhibition of LFA-1/intercellular adhesion molecule-1-mediated interactions between APCs and T cells dur ing sensitization induced long term, Ag-specific,hyporesponsiveness of mice to the hapten 2,4-dinitro-1-fluoro-benzene.