Neonatal exposure to antigen induces a defective CD40 ligand expression that undermines both IL-12 production by APC and IL-2 receptor up-regulation on splenic T cells and perpetuates IFN-γ-dependent T cell anergy

B. Min, K. L. Legge, J. J. Bell, R. K. Gregg, L. Li, J. C. Caprio, H. Zaghouani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

T cell deletion and/or inactivation were considered the leading mechanisms for neonatal tolerance. However, recent investigations have indicated that immunity develops at the neonatal stage but evolves to guide later T cell responses to display defective and/or biased effector functions. Although neonatal-induced T cell modulation provides a useful approach to suppress autoimmunity, the mechanism underlying the biased function of the T cells remains unclear. In prior studies, we found that exposure of newborn mice to Ig-PLP1, a chimera expressing the encephalitogenic proteolipid protein (PLP) sequence 139-151, induced deviated Th2 lymph node cells producing IL-4 instead of IL-2 and anergic splenic T cells that failed to proliferate or produce IFN-γ yet secreted significant amounts of IL-2. However, if assisted with IFN-γ or IL-12, these anergic splenic T cells regained full responsiveness. The consequence of such biased/defective T cells responses was protection of the mice against experimental allergic encephalomyelitis. In this study, investigations were performed to delineate the mechanism underlying the novel form of IFN-γ-dependent splenic anergy. Our findings indicate that CD40 ligand expression on these splenic T cells is defective, leading to noneffective cooperation between T lymphocytes and APCs and a lack of IL-12 production. More striking, this cellular system revealed a requirement for IL-2R expression for CD40 ligand-initiated, IL-12-driven progression of T cells into IFN-γ production.

Original languageEnglish (US)
Pages (from-to)5594-5603
Number of pages10
JournalJournal of Immunology
Volume166
Issue number9
DOIs
StatePublished - May 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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