Limits...
Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression.

Giese NA, Gabriele L, Doherty TM, Klinman DM, Tadesse-Heath L, Contursi C, Epstein SL, Morse HC - J. Exp. Med. (1997)

Bottom Line: In sera of normal mice, immunoglobulin (Ig)G2a antibodies were dominant over IgG1 antibodies, a pattern indicative of a T helper cell type 1 (Th1)-driven response.Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide.This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0760, USA. ngiese@atlas.niaid.nih.gov

ABSTRACT
Mice with a mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a chronic myelogenous leukemia-like syndrome and mount impaired responses to certain viral and bacterial infections. To gain a mechanistic understanding of the contributions of ICSBP to humoral and cellular immunity, we characterized the responses of control and ICSBP-/- mice to infection with influenza A (flu) and Leishmania major (L. major). Mice of both genotypes survived infections with flu, but differed markedly in the isotype distribution of antiflu antibodies. In sera of normal mice, immunoglobulin (Ig)G2a antibodies were dominant over IgG1 antibodies, a pattern indicative of a T helper cell type 1 (Th1)-driven response. In sera of ICSBP-/- mice, however, IgG1 antibodies dominated over IgG2a antibodies, a pattern indicative of a Th2-driven response. The dominance of IgG1 and IgE over IgG2a was detected in the sera of uninfected mice as well. A seeming Th2 bias of ICSBP-deficient mice was also uncovered in their inability to control infection with L. major, where resistance is known to be dependent on IL-12 and IFN-gamma as components of a Th1 response. Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide. Compromised Th1 differentiation in ICSBP-/- mice could not be attributed to hyporesponsiveness of CD4(+) T cells to interleukin (IL)-12; however, the ability of uninfected and infected ICSBP-deficient mice to produce IL-12 was markedly impaired. This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression.

Show MeSH

Related in: MedlinePlus

Distribution of serum Ig isotypes with the pattern of constitutive cytokine expression by spleen cells of ICSBP−/− mice. (A) Concentration of Ig isotypes in serum of intact ICSBP−/− (KO) and ICSBP+/+  (WT) mice as determined by ELISA. (B) RT-PCR analysis of cytokine  RNA expression in spleen of intact KO and WT mice. The mean ±  SEM for each group of mice is shown.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199114&req=5

Figure 1: Distribution of serum Ig isotypes with the pattern of constitutive cytokine expression by spleen cells of ICSBP−/− mice. (A) Concentration of Ig isotypes in serum of intact ICSBP−/− (KO) and ICSBP+/+ (WT) mice as determined by ELISA. (B) RT-PCR analysis of cytokine RNA expression in spleen of intact KO and WT mice. The mean ± SEM for each group of mice is shown.

Mentions: It is well established that Ths play a prominent role in regulating Ig isotype switching in response to T cell–dependent antigens. Th1s expressing IFN-γ strongly promote class switching to IgG2a and IgG3, whereas Th2s producing IL-4 strongly bias switching toward IgG1 and IgE (38). The isotype distributions of antiflu antibodies thus suggest a Th1-driven response by +/+ mice and a Th2-driven response by ICSBP-deficient mice. To determine whether similar biases were evident in the responses of these mice to environmental antigens, we examined the distribution of Ig isotypes in sera of uninfected wild-type and knockout mice (Fig. 1 A). The observations that the levels of IgG1 and IgE were markedly higher and the levels of IgG2a reduced in the sera of −/− mice compared with that of +/+ mice were consistent with the hypothesis of Th2 dominance in ICSBP−/− mice.


Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression.

Giese NA, Gabriele L, Doherty TM, Klinman DM, Tadesse-Heath L, Contursi C, Epstein SL, Morse HC - J. Exp. Med. (1997)

Distribution of serum Ig isotypes with the pattern of constitutive cytokine expression by spleen cells of ICSBP−/− mice. (A) Concentration of Ig isotypes in serum of intact ICSBP−/− (KO) and ICSBP+/+  (WT) mice as determined by ELISA. (B) RT-PCR analysis of cytokine  RNA expression in spleen of intact KO and WT mice. The mean ±  SEM for each group of mice is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199114&req=5

Figure 1: Distribution of serum Ig isotypes with the pattern of constitutive cytokine expression by spleen cells of ICSBP−/− mice. (A) Concentration of Ig isotypes in serum of intact ICSBP−/− (KO) and ICSBP+/+ (WT) mice as determined by ELISA. (B) RT-PCR analysis of cytokine RNA expression in spleen of intact KO and WT mice. The mean ± SEM for each group of mice is shown.
Mentions: It is well established that Ths play a prominent role in regulating Ig isotype switching in response to T cell–dependent antigens. Th1s expressing IFN-γ strongly promote class switching to IgG2a and IgG3, whereas Th2s producing IL-4 strongly bias switching toward IgG1 and IgE (38). The isotype distributions of antiflu antibodies thus suggest a Th1-driven response by +/+ mice and a Th2-driven response by ICSBP-deficient mice. To determine whether similar biases were evident in the responses of these mice to environmental antigens, we examined the distribution of Ig isotypes in sera of uninfected wild-type and knockout mice (Fig. 1 A). The observations that the levels of IgG1 and IgE were markedly higher and the levels of IgG2a reduced in the sera of −/− mice compared with that of +/+ mice were consistent with the hypothesis of Th2 dominance in ICSBP−/− mice.

Bottom Line: In sera of normal mice, immunoglobulin (Ig)G2a antibodies were dominant over IgG1 antibodies, a pattern indicative of a T helper cell type 1 (Th1)-driven response.Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide.This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0760, USA. ngiese@atlas.niaid.nih.gov

ABSTRACT
Mice with a mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a chronic myelogenous leukemia-like syndrome and mount impaired responses to certain viral and bacterial infections. To gain a mechanistic understanding of the contributions of ICSBP to humoral and cellular immunity, we characterized the responses of control and ICSBP-/- mice to infection with influenza A (flu) and Leishmania major (L. major). Mice of both genotypes survived infections with flu, but differed markedly in the isotype distribution of antiflu antibodies. In sera of normal mice, immunoglobulin (Ig)G2a antibodies were dominant over IgG1 antibodies, a pattern indicative of a T helper cell type 1 (Th1)-driven response. In sera of ICSBP-/- mice, however, IgG1 antibodies dominated over IgG2a antibodies, a pattern indicative of a Th2-driven response. The dominance of IgG1 and IgE over IgG2a was detected in the sera of uninfected mice as well. A seeming Th2 bias of ICSBP-deficient mice was also uncovered in their inability to control infection with L. major, where resistance is known to be dependent on IL-12 and IFN-gamma as components of a Th1 response. Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide. Compromised Th1 differentiation in ICSBP-/- mice could not be attributed to hyporesponsiveness of CD4(+) T cells to interleukin (IL)-12; however, the ability of uninfected and infected ICSBP-deficient mice to produce IL-12 was markedly impaired. This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression.

Show MeSH
Related in: MedlinePlus