Interleukin-12 but not interferon-gamma production correlates with induction of T helper type-1 phenotype in murine candidiasis

Eur J Immunol. 1994 Apr;24(4):909-15. doi: 10.1002/eji.1830240419.


By means of polymerase chain reaction-assisted mRNA amplification, we have monitored message levels of interleukin (IL)-12 in splenic macrophages and of interferon-gamma (IFN-gamma), IL-4, and IL-10 in CD4+ and CD8+ T cells using Candida albicans/host combinations that result either in a T helper type-1 (Th1)-associated self-limiting infection ("healer mice") or in a Th2-associated progressive disease ("nonhealer mice"). The timing and pattern of message detection did not differ qualitatively by the expression of IFN-gamma or IL-10 mRNA in CD4+ and CD8+ cells from healer (i.e. PCA-2 into CD2F1) vs. nonhealer (i.e. CA-6 into CD2F1 or PCA-2 into DBA/2) mice. In contrast, IL-4 mRNA was uniquely expressed by CD4+ cells from nonhealer animals. IL-12p40 was readily detected in macrophages from healer mice but was detected only early in infection in mice with progressive disease. Cytokine levels were measured in sera, and antigen-driven cytokine production by CD4+ and CD8+ cells was assessed in vitro, while IFN-gamma-producing cells were enumerated in CD4- CD8- cell fractions. Overall, our results showed that (i) antigen-specific secretion of IFN-gamma protein in vitro by CD4+ cells occurred only in healing infection; (ii) IL-4- and IL-10-producing CD4+ cells would expand in nonhealer mice in the face of high levels of circulating IFN-gamma, likely released by CD4- CD8- lymphocytes; (iii) a finely regulated IFN-gamma production correlated in the healer mice with IL-12 mRNA detection, and IL-12 was required in vitro for yeast-induced development of IFN-gamma-producing CD4+ cells. Although the mutually exclusive production of IL-4/IL-10 and IFN-gamma by early CD4+ cells may be the major discriminative factor of cure and noncure responses in candidiasis, IL-12 rather than IFN-gamma production may be an indicator of Th1 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Candidiasis / immunology*
  • Cells, Cultured
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-12
  • Interleukins / biosynthesis*
  • Interleukins / genetics
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Phenotype
  • RNA, Messenger / analysis
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Interleukins
  • RNA, Messenger
  • Interleukin-12
  • Interferon-gamma