Specific antibodies induced by DNA vaccination with extracellular domain of CD25 gene protect against ConA-induced autoimmune hepatitis.
Antibodies to CD25 (anti-CD25) were used clinically to achieve immunosuppression in autoimmune disease, while the possibility of anti-antibodies generation influenced its efficiency. Here we reported that DNA vaccine encoding the extracellular domain of murine CD25 gene (pCD25-ECD) elicited anti-CD25 antibody production in BALB/c mice and subsequently prevents the host against ConA-induced autoimmune hepatitis. We found that serum CD25-specific antibodies were generated after vaccination with pCD25-ECD. Moreover, high levels of IL-4, IL-10 and anti-CD25 antibody were produced by splenocytes of vaccinated mice after CD25 protein restimulation in vitro. Furthermore, we demonstrated that the vaccinated mice suffered less from liver injury induced by ConA, accompanied by the reduction of pathogenic CD4+ T cells. Finally, we showed that the immunized serum could cause cytolysis of activated CD4+ T cells in vitro, depending on complements activation. Our study showed pCD25-ECD induced self anti-CD25 antibodies which executed immunosuppression in autoimmune hepatitis via antibody-complement pathway.
Xu
Lin
L
Institute for ImmunoBiology and Department of Immunology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Zhang
Feng
F
Xu
Wei
W
Xiong
Sidong
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003171:Complement Pathway, Classical / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D016207:Cytokines; C508018:Il2ra protein, mouse; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D003208:Concanavalin A; D000410:Alanine Transaminase