Soluble CD4 suppresses T-dependent IgG2a antibody response of CD4 loosing mice by inhibiting IFNgamma production.
To analyze the role of soluble CD4 (sCD4) in antibody (Ab) responses in CD4 loosing (CD4L) mice, experiments have been done in comparing CD4L mice with CD4 knockout (CD4KO) mice on the same C57BL/6 background. The CD4L mice have a defect in CD4 expression where CD4 mRNA is alternatively spliced so that a transmembrane portion is deleted and sCD4 are secreted without expression of membrane-bound CD4. Significantly reduced immunoglobulin (Ig) G2a isotype Ab response against a T-dependent antigen (Ag), trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), was found in CD4L mice as compared with those of CD4KO mice. Gamma interferon (IFNgamma) production of KLH-stimulated lymph nodes cells was significantly reduced in CD4L mice as compared with those in CD4KO mice. The positive proportion of cells expressing CD40 ligand from CD4KO mice or CD4L mice was much lower than those from wild type mice. There was no difference between CD4KO and CD4L mice in T-cells expressing CD40 ligand after stimulation. Taken together, results in this study indicate that sCD4 suppresses IgG2a Ab 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 Ab response against T-dependent Ag.
Wang
C R
CR
Department of Internal Medicine, National Cheng-Kung University Medical College, Tainan, Taiwan, ROC.
D000818:Animals; D015704:CD4 Antigens / Q000494:pharmacology*; D019013:CD40 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D005453:Fluorescence; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology*; D013997:Time Factors
D015704:CD4 Antigens; D019013:CD40 Antigens; D007074:Immunoglobulin G; D008024:Ligands; D011994:Recombinant Proteins; C076613:recombinant soluble CD4; D007371:Interferon-gamma