Endogenous interleukin-4 downregulates the type 1 CD4 T cell-mediated immune response induced by intramuscular DNA immunization.
Intramuscular (i.m.) administration of eukaryotic plasmid vectors containing foreign genes is a general immunization strategy capable of inducing protective type 1 immune responses against viral, bacterial, fungal, and parasitic infections. We have described that immunization with a plasmid containing a gene encoding a parasite antigen elicits specific type 1 protective immune responses against experimental infection with the human protozoan parasite Trypanosoma cruzi. However, we had evidence suggesting that DNA immunization concomitantly activated specific type 2 immune responses. To determine precisely the influence of the type 2 cytokine interleukin-4 (IL-4) during DNA immunization, we compared the immune responses of genetically modified IL-4-deficient or wild-type (wt) BALB/c mice. IL-4-deficient mice had a significantly lower ratio of specific serum IgG1/IgG2a, and on in vitro restimulation with antigen, their spleen cells secreted significantly higher amounts of interferon-gamma (IFN-gamma). In contrast, absence of IL-4 did not affect total serum antibody response, T cell proliferative responses, or activation of IFN-gamma-producing CD8(+) T cells. Our results suggested that in contrast to conventional adjuvants, such as alum and complete Freund's adjuvant, specific IgG1 in DNA-immunized BALB/c mice was highly dependent on IL-4. To our knowledge, our study provides the first evidence that endogenous IL-4 selectively downregulates the type 1 CD4(+) T cell-mediated immune response induced by i.m. genetic immunization, a fact that may have implications for the design of certain DNA vaccines.
Rodrigues
Mauricio M
MM
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP, Brazil, 04023-062. mrodrigues@ecb.epm.br
Soares
Milena B P
MB
Vasconcelos
José Ronnie C
JR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000494:pharmacology*
D007074:Immunoglobulin G; D019444:Vaccines, DNA; D015847:Interleukin-4