Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Source: T cells (TH1, CD8+ T cells), NK cells

Interferon-gamma effects

- Macrophages: activation (increased microbicidal functions)
- B cells: isotype switching to opsonizing and complement-fixing IgG subclasses
- T cells: TH1 differentiation
- Various cells: increased expression of class I and class II MHC molecules, increased antigen processing and presentation to T cells

Interferon-gamma suppresses TH2-cell-mediated allergic inflammation and suppresses allergic airway inflammation in animal models. It is induced during SCIT.

What is T-bet?

T-bet (also called TBX21 or T-box 21) is pivotal for Th1 maturation. STAT4 activates the transcription factor T-bet, which induces the secretion of IFN-gamma. T-bet promotes Th1 development by direct induction of IFN-gamma and IL-12Rbeta2 chain gene transcription. IFN-gamma acts an amplifier by binding to its receptor on Th1 cells and activating STAT1, which then engages T-bet. T-bet is a bridge between innate and adaptive immunity (

T-bet inhibits IL-4, IL-5, and IL-17 secretion. T-bet may also inhibit Th2 differentiation by preventing GATA3 from interacting with its target DNA.

Potential treatment targets

T-bet: CpG antisense oligodeoxynucleotides

GATA3: GATA3-specific DNAzyme and CpG antisense oligodeoxynucleotides

Interferon-gamma therapy in asthma

Early studies of recombinant human IFN gamma gamma SQ in asthma were disappointing. One small study showed a reversal of the TH2-cell cytokine profile in severe asthma.

IFN beta therapy in asthma

Epithelial cells from asthmatics have an impaired protective IFNb response to infection with the common cold virus. Trials of recombinant human IFNb by inhalation to prevent severe virus-induced asthma exacerbations.

What is IGRA?

Interferon Gamma Release Assay (IGRA): used in any evaluation for TB infection (active or latent). It is more specific than TSTs (PPD), which may be positive with previous BCG or exposure to non-TB Mb. A positive test indicates TB infection. A negative test excludes TB in immunocompetent patients.


Hwang ES; Szabo SJ; Schwartzberg PL; Glimcher LH. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 2005 Jan 21;307(5708):430-3.

Boguniewicz, M. et al. The effects of nebulized recombinant interferon-γ in asthmatic airways. J. Allergy Clin. Immunol. 95, 133–135 (1995).

Simon, H. U., Seelbach, H., Ehmann, R. & Schmitz, M. Clinical and immunological effects of low-dose IFNα treatment in patients with corticosteroid-resistant asthma. Allergy 58, 1250–1255 (2003).

Wark, P. A. et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J. Exp. Med. 201, 937–947 (2005).

Contoli, M. et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nature Med. 12, 1023–1026 (2006).

Holgate, S. T. Exacerbations: the asthma paradox. Am. J. Respir. Crit. Care Med. 172, 941–943 (2005).

Prognostic Value of a T-Cell–Based, Interferon- Biomarker in Children with Tuberculosis Contact Mustafa Bakir, MD; Kerry A. Millington, DPhil; Ahmet Soysal, MD; Jonathan J. Deeks, PhD; Serpil Efee; Yasemin Aslan, SRN; Davinder P.S. Dosanjh, DPhil; and Ajit Lalvani, DM. Annals of Int Med, 2 December 2008 | Volume 149 Issue 11 | Pages 777-786.

Neonatal BCG vaccination induces IL-10 production by CD4(+) CD25(+) T cells.

Related reading

Protective effect of BCG vaccination: time to reconsider the vaccination threshold? Thorax, 2010.
BCG vaccination: 90 years on and still so much to learn - Thorax

Published: 04/09/2010
Updated: 04/09/2011

No comments: