Interferon-alpha regulates the dynamic balance between human activated regulatory and effector T cells: Implications for antiviral and autoimmune responses

Amit Golding, Antony Rosen, Michelle Petri, Ehtisham Akhter, Felipe Andrade

Research output: Contribution to journalArticlepeer-review

Abstract

An adequate effector response against pathogens and its subsequent inactivation after pathogen clearance are critical for the maintenance of immune homeostasis. This process involves an initial phase of T-cell effector (Teff) activation followed by the expansion of regulatory T cells (Tregs), a unique cell population that limits Teff functions. However, significant questions remain unanswered about the mechanisms that regulate the balance between these cell populations. Using an in vitro system to mimic T-cell activation in human peripheral blood mononuclear cells (PBMC), we analysed the patterns of Treg and Teff activation, with special attention to the role of type I interferon (IFN-I). Interestingly, we found that IFN-α, either exogenously added or endogenously induced, suppressed the generation of CD4+ FoxP3 HIIFN-γNeg activated Tregs (aTregs) while simultaneously promoting propagation of CD4+ FoxP3 Low/NegIFN-γPos activated Teffs (aTeffs). We also showed that IFN-α-mediated inhibition of interleukin (IL)-2 production may play an essential role in IFN-α-induced suppression of aTregs. In order to test our findings in a disease state with chronically elevated IFN-α, we investigated systemic lupus erythematosus (SLE). Plasma from patients with SLE was found to contain IFN-I activity that suppressed aTreg generation. Furthermore, anti-CD3 activated SLE PBMCs exhibited preferential expansion of aTeffs with a very limited increase in aTreg numbers. Together, these observations support a model whereby a transient production of IFN-α (such as is seen in an early antiviral response) may promote CD4 effector functions by delaying aTreg generation, but a chronic elevation of IFN-α may tip the aTeff:aTreg balance towards aTeffs and autoimmunity.

Original languageEnglish (US)
Pages (from-to)107-117
Number of pages11
JournalImmunology
Volume131
Issue number1
DOIs
StatePublished - Sep 2010

Keywords

  • activation
  • autoimmunity
  • innate immunity
  • regulatory T cells (Tregs)
  • viruses/viral immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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