Impaired delayed‐type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane‐bound CD4

Wang, C.-R.; Hino, Ayako; Yoshimoto, Takayuki; Nagase, Hisashi; Kato, Takuma; Hirokawa, Katsuíku; Matsubara, Akio; Nariuchi, Hideo

doi:10.1046/j.1365-2567.2000.00055.x

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…However, injection of anti-CD4 mAb restored DTH response, suggesting that the soluble CD4 is responsible for suppression. 17) Similarly, soluble CD4 prevented a host resistance DTH response to infection with Cryptococcus neoformans in mutant mice. 18) Thus, soluble CD4 suppresses DTH response in these experimental models.…”

Section: Discussionmentioning

confidence: 98%

Immune Responses in Resistant and Susceptible Strains of CD4-Mutant Mice Infected with Leishmania major

Yamakami

Oda

Watanabe

et al. 2005

JOURNAL OF HEALTH SCIENCE

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We examined the immune response of CD4-mutant mice that have soluble form of CD4 in the circulation without expression of CD4 on T cell surface. We infected the CD4-mutant mice of BALB/c and C57BL/6 backgrounds with Leishmania major and subsequently examined parameters of disease and immune response. In contrast to wild-type (wt) BALB/c mice, mutant mice of both strains showed decreased parasite replication and an intense leishmanial antigen-specific delayed-type hypersensitivity (DTH) response. In vitro cytokine analysis revealed that popliteal lymph node cells (LNC) from mutant mice of both strains secreted little or no detectable interleukin-4 (IL-4) and they secreted interferon-γ (IFN-γ) at levels similar to those of wt mice. The cytokine profile shows that a lack of IL-4 production underlies the lack of T helper type 2 (Th2) response. As validation of the impaired Th2 response, infection of the mice with Nippostrongylus brasiliensis, a typical Th2 inducer, showed a lack of Th2 response. Furthermore, in contrast to LNC from wt mice, Th2 cells were not induced from naive LNC of mutant mice when the cells were cultured in the presence of IL-4 and anti-IL-12 antibody. These findings indicate that the lack of IL-4 production is due to a lack of CD4 on T cells and that IFN-γ production is independent of CD4 on T cells. Thus, Th1 and Th2 responses to leishmanial infection are not due to the balance of IL-4/IFN-γ that are produced, but the production of IL-4 determines whether a Th1 or Th2 response will develop.

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Section: Discussionmentioning

confidence: 98%

Immune Responses in Resistant and Susceptible Strains of CD4-Mutant Mice Infected with Leishmania major

Yamakami

Oda

Watanabe

et al. 2005

JOURNAL OF HEALTH SCIENCE

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“…The antibody results reveal that both adjuvant groups exhibited excellent humoral responses throughout the whole experiment, whereas the IgG and IgG isotype levels induced by the E515- Bb vaccine were superior to those induced by the Alum- Bb vaccine, and the antibody response peaked at 14 days post-boost ( Figure 2 A). Soluble CD4 and CD8 have been suggested to be released into the serum from activated CD4 and CD8 T cells [ 36 , 37 ]. Bacterial vaccines can reportedly enhance the activities of both CD4 and CD8 T cells and result in better protective immunity [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of the Bordetella bronchiseptica Vaccine Combined with a Vegetable Oil Adjuvant and Multi-Omics Analysis of Its Potential Role in the Protective Response of Rabbits

Cui

Huang

et al. 2022

Pharmaceutics

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Infectious respiratory diseases caused by Bordetella bronchiseptica (Bb) are seriously endangering the development of the rabbit industry in China. Unfortunately, no licensed vaccines are available for this pathogen. The present study was designed to determine whether the inactivated Bb antigen formulated with vegetable oil adjuvant (named E515) which contains soybean oil, vitamin E, and ginseng saponins, functions as a safe and effective vaccine (E515-Bb) against Bb infection in rabbits. Based on local and systemic reactions, both the E515 adjuvant alone and the E515-Bb vaccine exhibited good safety in rabbits. Immune response analysis implies that rabbits immunized with the E515-Bb vaccine produced significantly higher, earlier, and longer-lasting specific antibody responses and activated Th1/Th2/Th17 cell responses than those immunized with the aluminum hydroxide (Alum)-adjuvanted Bb vaccine (Alum-Bb) or Bb antigen alone. Moreover, the E515-Bb vaccine effectively protected rabbits from Bb infection. Additionally, integrated multi-omics analysis revealed that the immunoprotective effect of the E515-Bb vaccine was achieved through upregulation of the complement and coagulation cascades and cell adhesion molecule (CAM) pathways, and the downregulation of the P53 pathway. Overall, these results indicate that the E515-Bb vaccine is safe, elicits an efficient immune response and provides good protection against Bb infection in rabbits. Thus, the E515-adjuvanted Bb vaccine can be considered a promising candidate vaccine for preventing Bb infection.

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“…However, the lack of CD4 transmembrane region was reported for a mutant mouse model that secreted soluble CD4 without expression of membrane-bound CD4 [ 19 ]. This mouse model was used to show that soluble CD4 impaired a delayed-type hypersensitivity response by inhibiting IFN-γ production, and prohibited over-activation of CD4+ T cells by competitive inhibition of the binding of CD4 on the T-cell surface to MHC class II [ 20 ]. So, if the exon 8 deficiency forms are translated to the protein, the secreted CD4 might be also associated with prohibiting over-activation of CD4+ T cells in swine.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of two CD4 alleles in Microminipigs

et al. 2016

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BackgroundWe previously identified two phenotypes of CD4+ cells with and without reactions to anti-pig CD4 monoclonal antibodies by flow cytometry in a herd of Microminipigs. In this study, we analyzed the coding sequences of CD4 and certified the expression of CD4 molecules in order to identify the genetic sequence variants responsible for the positive and negative PBMCs reactivity to anti-pig CD4 monoclonal antibodies.ResultsWe identified two CD4 alleles, CD4.A and CD4.B, corresponding to antibody positive and negative, respectively, by nucleotide sequencing of PCR products using CD4 specific primer pairs. In comparison with the swine CD4 amino-acid sequence [GenBank: NP_001001908], CD4.A had seven amino-acid substitutions and CD4.B had 15 amino-acid substitutions. The amino-acid sequences within domain 1 of CD4.B were identical to the swine CD4.2 [GenBank: CAA46584] sequence that had been reported previously to be a modified CD4 molecule that had lost reactivity with an anti-pig CD4 antibody in NIH miniature pigs. Homozygous and heterozygous CD4.A and CD4.B alleles in the Microminipigs herd were characterised by using the RFLP technique with the restriction endonuclease, BseRI. The anti-pig CD4 antibody recognized pig PBMCs with CD4.AA and CD4.AB, but did not recognized those with CD4.BB. We transfected HeLa cells with the FLAG-tagged CD4.A or CD4.B vectors, and certified that transfected HeLa cells expressed FLAG in both vectors. The failure of cells to react with anti-CD4 antibodies in CD4.B pigs was associated to ten amino-acid substitutions in domain 1 and/or one amino-acid substitution in joining region 3 of CD4.B. We also found exon 8 was defective in some CD4.A and CD4.B resulting in the loss of the transmembrane domain, which implies that these CD4 proteins are secreted from helper T cells into the circulation.ConclusionsWe identified that amino-acids substitutions of domain 1 in CD4.B gave rise to the failure of some CD4 expressing cells to react with particular anti-pig CD4 monoclonal antibodies. In addition, we developed a PCR-RFLP method that enabled us to simply identify the CD4 sequence variant and the positive and negative PBMCs reactivity to our anti-pig CD4 monoclonal antibodies without the need to use flow cytometric analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0856-8) contains supplementary material, which is available to authorized users.

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Impaired delayed‐type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane‐bound CD4

Cited by 5 publications

References 30 publications

Immune Responses in Resistant and Susceptible Strains of CD4-Mutant Mice Infected with Leishmania major

Immune Responses in Resistant and Susceptible Strains of CD4-Mutant Mice Infected with Leishmania major

Safety and Efficacy of the Bordetella bronchiseptica Vaccine Combined with a Vegetable Oil Adjuvant and Multi-Omics Analysis of Its Potential Role in the Protective Response of Rabbits

Identification and characterization of two CD4 alleles in Microminipigs

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