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Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.

Kopf M, Coyle AJ, Schmitz N, Barner M, Oxenius A, Gallimore A, Gutierrez-Ramos JC, Bachmann MF - J. Exp. Med. (2000)

Bottom Line: Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development.In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS.Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+) subset (Th1 and Th2) responses but not CTL responses in vivo.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, 4005 Basel, Switzerland. kopf@bii.ch

ABSTRACT
It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+) subset (Th1 and Th2) responses but not CTL responses in vivo.

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Blocking ICOS does not affect antibody isotype switching after infection with LCMV. CD28−/− mice and C57BL/6 control mice (BL6) were infected with 200 PFU LCMV) and treated with ICOS-Ig or control IgG1 (solid bars) starting at day 0 every 2 d until day 10. Blood was taken 12 d after infection, and LCMV-specific IgG1, IgG2a, and IgG2b titers were determined by ELISA. Data are representative of two separate experiments.
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Figure 4: Blocking ICOS does not affect antibody isotype switching after infection with LCMV. CD28−/− mice and C57BL/6 control mice (BL6) were infected with 200 PFU LCMV) and treated with ICOS-Ig or control IgG1 (solid bars) starting at day 0 every 2 d until day 10. Blood was taken 12 d after infection, and LCMV-specific IgG1, IgG2a, and IgG2b titers were determined by ELISA. Data are representative of two separate experiments.

Mentions: ICOS has been reported to be expressed by germinal center T cells 10. Therefore, it was conceivable that it is critically involved in the regulation of Th cell–dependent B cell responses. To assess this question, we measured specific IgG antibody levels in response to LCMV infection in the various groups of mice. IgG1, IgG2a, and IgG2b antibody responses were reduced 5–10-fold in CD28-deficient mice, but were not affected in C57BL/6 mice treated with ICOS-Fc (Fig. 4). Surprisingly, neutralization of ICOS in CD28-deficient mice did not further reduce specific antibody levels (Fig. 4), despite reduced CD4+ T cell proliferation and IFN-γ production in this situation.


Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.

Kopf M, Coyle AJ, Schmitz N, Barner M, Oxenius A, Gallimore A, Gutierrez-Ramos JC, Bachmann MF - J. Exp. Med. (2000)

Blocking ICOS does not affect antibody isotype switching after infection with LCMV. CD28−/− mice and C57BL/6 control mice (BL6) were infected with 200 PFU LCMV) and treated with ICOS-Ig or control IgG1 (solid bars) starting at day 0 every 2 d until day 10. Blood was taken 12 d after infection, and LCMV-specific IgG1, IgG2a, and IgG2b titers were determined by ELISA. Data are representative of two separate experiments.
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Related In: Results  -  Collection

Show All Figures
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Figure 4: Blocking ICOS does not affect antibody isotype switching after infection with LCMV. CD28−/− mice and C57BL/6 control mice (BL6) were infected with 200 PFU LCMV) and treated with ICOS-Ig or control IgG1 (solid bars) starting at day 0 every 2 d until day 10. Blood was taken 12 d after infection, and LCMV-specific IgG1, IgG2a, and IgG2b titers were determined by ELISA. Data are representative of two separate experiments.
Mentions: ICOS has been reported to be expressed by germinal center T cells 10. Therefore, it was conceivable that it is critically involved in the regulation of Th cell–dependent B cell responses. To assess this question, we measured specific IgG antibody levels in response to LCMV infection in the various groups of mice. IgG1, IgG2a, and IgG2b antibody responses were reduced 5–10-fold in CD28-deficient mice, but were not affected in C57BL/6 mice treated with ICOS-Fc (Fig. 4). Surprisingly, neutralization of ICOS in CD28-deficient mice did not further reduce specific antibody levels (Fig. 4), despite reduced CD4+ T cell proliferation and IFN-γ production in this situation.

Bottom Line: Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development.In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS.Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+) subset (Th1 and Th2) responses but not CTL responses in vivo.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, 4005 Basel, Switzerland. kopf@bii.ch

ABSTRACT
It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+) subset (Th1 and Th2) responses but not CTL responses in vivo.

Show MeSH
Related in: MedlinePlus