Soluble CD4 suppresses delayed-type hypersensitivity reaction of CD4 loosing mice by inhibiting INFgamma production.
The CD4 loosing (CD4L) mice have a novel defect in CD4 expression where CD4 mRNA is alternatively spliced to delete a transmembrane portion to give rise to the secretion of soluble CD4 (sCD4) without the expression of membrane-bound CD4. To analyze the role of sCD4 in immune responses in CD4L mice, experiments have been done by comparing CD4L mice with CD4 knockout (CD4KO) mice on the same C57BL/6 background. Significantly reduced delayed-type hypersensitivity (DTH) response against methylated BSA (mBSA) was found in CD4L mice; however, CD4KO mice showed a comparable response to wild type mice. Anti-CD4 treatment in CD4L mice could restore DTH response. Moreover, implantation of CD4KO mice with a diffusion chamber containing sCD4 secreting cells suppressed DTH response. DTH response recovered by anti-CD4 treatment in CD4L mice was inhibited by anti-interferon gamma (IFNgamma). IFNgamma production of mBSA-stimulated lymph node cells was significantly reduced in CD4L mice as compared with that in CD4KO or wild type mice, and the reduction could be recovered by the anti-CD4 treatment. IFNgamma production of mBSA-stimulated lymph node cells was suppressed in CD4KO mice carrying a diffusion chamber containing sCD4 secreting cells as compared with those containing control cells. Taken together, results in this study strongly indicate that sCD4 suppresses DTH responses of CD4L mice by inhibiting IFNgamma production. The mutant mice could provide a good model to analyze the mechanism of IFNgamma involvement in the DTH response.
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC.
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Wang
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology*; D006968:Hypersensitivity, Delayed / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007371:Interferon-gamma