Cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibits CD28-induced IκBα degradation and RelA activation

Claudio Pioli, Lucia Gatta, Daniela Frasca, Gino Doria

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Purified CD4+ cells from the spleens of C57BL/6 mice were stimulated with anti-CD3, anti-CD28 and anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibodies. The results show that CTLA-4 stimulation inhibits IL-2 production induced by CD3-CD28 cc-stimulation. Since CD3-CD28 co-stimulation induces IκBα degradation and consequently activates RelA, an NfκB family member relevant for the induction of IL-2 mRNA transcription, we tested whether the inhibitory effect of CTLA-4 stimulation interferes with this mechanism. CD3-CD28 co-stimulation was found to induce a drastic decrease in cytoplasmic IκBα and increase in nuclear RelA. CTLA-4 stimulation abrogates this effect of co-stimulation by increasing the level of cytoplasmic IκBα and decreasing the nuclear RelA level and DNA-binding activity. In conclusion, our results indicate that the inhibitory effect of CTLA-4 engagement on cytokine production correlates with prevention of IκBα degradation and inhibition of RelA nuclear translocation.

Original languageEnglish
Pages (from-to)856-863
Number of pages8
JournalEuropean Journal of Immunology
Volume29
Issue number3
StatePublished - Mar 18 1999
Externally publishedYes

Fingerprint

CTLA-4 Antigen
Interleukin-2
Inbred C57BL Mouse
Spleen
Monoclonal Antibodies
Cytokines
Messenger RNA
DNA

Keywords

  • CD28
  • CTLA-4
  • IκBα
  • IL-2
  • RelA

ASJC Scopus subject areas

  • Immunology

Cite this

Cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibits CD28-induced IκBα degradation and RelA activation. / Pioli, Claudio; Gatta, Lucia; Frasca, Daniela; Doria, Gino.

In: European Journal of Immunology, Vol. 29, No. 3, 18.03.1999, p. 856-863.

Research output: Contribution to journalArticle

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AU - Doria, Gino

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N2 - Purified CD4+ cells from the spleens of C57BL/6 mice were stimulated with anti-CD3, anti-CD28 and anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibodies. The results show that CTLA-4 stimulation inhibits IL-2 production induced by CD3-CD28 cc-stimulation. Since CD3-CD28 co-stimulation induces IκBα degradation and consequently activates RelA, an NfκB family member relevant for the induction of IL-2 mRNA transcription, we tested whether the inhibitory effect of CTLA-4 stimulation interferes with this mechanism. CD3-CD28 co-stimulation was found to induce a drastic decrease in cytoplasmic IκBα and increase in nuclear RelA. CTLA-4 stimulation abrogates this effect of co-stimulation by increasing the level of cytoplasmic IκBα and decreasing the nuclear RelA level and DNA-binding activity. In conclusion, our results indicate that the inhibitory effect of CTLA-4 engagement on cytokine production correlates with prevention of IκBα degradation and inhibition of RelA nuclear translocation.

AB - Purified CD4+ cells from the spleens of C57BL/6 mice were stimulated with anti-CD3, anti-CD28 and anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibodies. The results show that CTLA-4 stimulation inhibits IL-2 production induced by CD3-CD28 cc-stimulation. Since CD3-CD28 co-stimulation induces IκBα degradation and consequently activates RelA, an NfκB family member relevant for the induction of IL-2 mRNA transcription, we tested whether the inhibitory effect of CTLA-4 stimulation interferes with this mechanism. CD3-CD28 co-stimulation was found to induce a drastic decrease in cytoplasmic IκBα and increase in nuclear RelA. CTLA-4 stimulation abrogates this effect of co-stimulation by increasing the level of cytoplasmic IκBα and decreasing the nuclear RelA level and DNA-binding activity. In conclusion, our results indicate that the inhibitory effect of CTLA-4 engagement on cytokine production correlates with prevention of IκBα degradation and inhibition of RelA nuclear translocation.

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