Differential requirement of CD28 for IL-12 receptor expression and function in CD4(+) and CD8(+) T cells

Eur J Immunol. 2001 Feb;31(2):384-95. doi: 10.1002/1521-4141(200102)31:2<384::aid-immu384>3.0.co;2-9.

Abstract

IL-12 is a potent inducer of IFN-gamma production and Th1 responses. Co-stimulation mediated by B7 has been shown to synergize with IL-12 for optimal IFN-gamma production and proliferation in vitro. In this study, we examined the requirement of CD28/B7 interactions for optimal induction of IL-12 receptor(R) beta1 and beta2 expression and IFN-gamma. IL-12-induced IFN-gamma production and STAT4 nuclear translocation were markedly reduced in CD28(-/-) splenocytes compared to that of wild-type (WT) splenocytes. Analysis of IL-12R expression revealed that IL-12 induced similar levels of IL-12R beta2 mRNA expression in WT and CD28(-/-) cells. In contrast, IL-12R beta1 expression was impaired in CD28(-/-) cells, indicating that expression of IL-12R beta1 and beta2 is differentially regulated by CD28. CD28(-/-) CD4(+) but not CD8(+) cells exhibited a defect in IL-12Rbeta1 expression that was associated with a marked decrease in IL-12 binding as well as IL-12-induced IFN-gamma production. IL-2 could restore IL-12R expression to CD28(-/-) CD4(+) cells, however, this occurred independently of IL-2-induced proliferation. Thus, these findings identify distinct requirements for CD28 in the capacity of CD4(+) and CD8(+) cells to respond maximally to IL-12.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD28 Antigens / physiology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • DNA-Binding Proteins / physiology
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / pharmacology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • Trans-Activators / physiology

Substances

  • CD28 Antigens
  • DNA-Binding Proteins
  • Il12rb1 protein, mouse
  • Il12rb2 protein, mouse
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • Stat4 protein, mouse
  • Trans-Activators
  • Interleukin-12
  • Interferon-gamma