Antony Rosen

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

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 (Profiled Authors: Felipe Andrade; Michelle Petri; Antony Rosen)

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Immunology 2010;131(1):107-17.

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-alpha, either exogenously added or endogenously induced, suppressed the generation of CD4(+) FoxP3(HI )IFN-gamma(Neg) activated Tregs (aTregs) while simultaneously promoting propagation of CD4(+) FoxP3(Low/Neg )IFN-gamma(Pos) activated Teffs (aTeffs). We also showed that IFN-alpha-mediated inhibition of interleukin (IL)-2 production may play an essential role in IFN-alpha-induced suppression of aTregs. In order to test our findings in a disease state with chronically elevated IFN-alpha, 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-alpha (such as is seen in an early antiviral response) may promote CD4 effector functions by delaying aTreg generation, but a chronic elevation of IFN-alpha may tip the aTeff:aTreg balance towards aTeffs and autoimmunity.

Scientific Context

This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.