Hyporesponsiveness in contact hypersensitivity and irritant contact dermatitis in CD4 gene targeted mouse.
To determine the role of CD4 molecules in the generation and regulation of contact hypersensitivity (CHS), we treated mice lacking the CD4 gene as a result of targeted disruption with dinitrofluorobenzene to induce CHS. The mutant mice lacking CD4 (CD4(-) mice) showed marked hyporesponsiveness 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 swelling; 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 sensitized normal mice restored the responsiveness in CD4(-) mice, but those from sensitized CD4(-) mice were less effective in restoring the CHS response in normal mice. Langerhans cell numbers were normal, and function, as assessed by the ability to present soluble hapten, was not impaired in CD4(-) mice. Skin cytokine profiles demonstrated an increase in interferon-gamma, interleukin-2, and interleukin-4 mRNA levels after challenge in normal mice, whereas this response was blunted in CD4(-) mice. CD4(-) mice also showed hyporesponsiveness in inflammatory reaction to irritant chemicals. These results suggest that the CD4 molecule is required for optimal induction of CHS as well as irritant contact dermatitis and may influence the development of CHS by modulating the cytokine profiles in the skin.
Kondo
S
S
Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Canada.
Beissert
S
S
Wang
B
B
Fujisawa
H
H
Kooshesh
F
F
Stratigos
A
A
Granstein
R D
RD
Mak
T W
TW
Sauder
D N
DN
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000235:genetics; D003877:Dermatitis, Contact / Q000209:etiology*; D017453:Dermatitis, Irritant / Q000209:etiology*; D004139:Dinitrofluorobenzene; D005260:Female; D007801:Langerhans Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis
D015704:CD4 Antigens; D016207:Cytokines; D012333:RNA, Messenger; D004139:Dinitrofluorobenzene