Interleukin 12 suppresses autoantibody production by reversing helper T-cell phenotype in hepatitis B e antigen transgenic mice.
Helper T (Th) cells are classified as Th1 or Th2 cells by virtue of cytokine secretion and function as mediators of cellular or humoral immunity, respectively. Cytokines also regulate the differentiation of Th cells. For example, interleukin (IL)-12 promotes Th1 and suppresses Th2 cell development, suggesting that IL-12 may be useful therapeutically in Th2-mediated autoimmune and allergic disorders. Therefore, the effect of systemic IL-12 treatment on in vivo autoantibody synthesis in hepatitis B e antigen (HBeAg)-expressing transgenic mice, which is dependent on self-reactive Th2 cells, was examined. Low-dose IL-12 significantly inhibited autoantibody production by shifting the Th2-mediated response toward Th1 predominance. Additionally, previous studies suggest that a predominance of HBeAg-specific Th2-type cells may contribute to chronicity in hepatitis B virus infection. Therefore, IL-12 may also prove beneficial in modulating the HBeAg-specific Th response to favor viral clearance in chronic hepatitis B virus infection.
Milich
D R
DR
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Wolf
S F
SF
Hughes
J L
JL
Jones
J E
JE
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000628:therapy; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000494:pharmacology; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000914:Antibodies, Viral; D001323:Autoantibodies; D016207:Cytokines; D006513:Hepatitis B e Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins; D018664:Interleukin-12