HYPORESPONSIVENESS IN CONTACT HYPERSENSITIVITY AND IRRITANT CONTACT-DERMATITIS IN CD4 GENE TARGETED MOUSE

To determine the role of CD4 molecules in the generation and regulatio n of contact hypersensitivity (CHS), we treated mice lacking the CD4 g ene as a result of targeted disruption with dinitrofluorobenzene to in duce CHS. The mutant mice lacking CD4 (CD4(-) mice) showed marked hypo responsiveness in CHS compared with normal syngeneic C57BL/6 mice (38. 3 +/- 9.0% of normal at 24 h after the challenge assessed by net ear s welling; p < 0.025), CD4(-) mice had a larger CD4-8- double negative T -cell receptor alpha beta+ cell population in the lymph nodes than did normal mice, and the increase of this cell population was observed in CD4(-) mice after sensitization. Draining lymph node cells from sensi tized normal mice restored the responsiveness in CD4(-) mice, but thos e from sensitized CD4(-) mice were less effective in restoring the CHS response in normal mice. Langerhans cell numbers were normal, and fun ction, as assessed by the ability to present soluble hapten, was not i mpaired in CD4(-) mice. Skin cytokine profiles demonstrated an increas e in interferon-gamma, interleukin-2, and interleukin-4 mRNA levels af ter challenge in normal mice, whereas this response was blunted in CD4 (-) mice, CD4(-) mice also showed hyporesponsiveness in inflammatory r eaction to irritant chemicals. These results suggest that the CD4 mole cule is required for optimal induction of CHS as well as irritant cont act dermatitis and may influence the development of CHS by modulating the cytokine profiles in the skin.