IL-2/anti-IL-2 antibody complex treatment inhibits the development but not the progression of herpetic stromal keratitis

J Immunol. 2015 Jan 1;194(1):273-82. doi: 10.4049/jimmunol.1401285. Epub 2014 Nov 19.


The IL-2/anti-IL-2 Ab immunocomplex has recently been shown to expand the naturally occurring pool of CD4(+)Foxp3(+) regulatory T cells (Tregs). In this study, we show that administration of the IL-2/anti-IL-2 Ab immunocomplex to C57BL/6 mice, prior to corneal HSV-1 infection, significantly increased the pool of Foxp3(+) Tregs when measured at early time points postinfection. Increased numbers of Foxp3(+) Tregs on days 2 and 4 postinfection resulted in a marked reduction in the development of severe herpetic stromal keratitis (HSK). When compared with corneas from the control group, corneas from the immunocomplex-treated group showed a significant reduction in the amount of infectious virus on day 2 but not on day 4 postinfection. Reduced viral load was associated with a 2-fold increase in NK cell numbers in corneas from the immunocomplex-treated group of mice. Moreover, a dramatic reduction in the influx of CD4 T cells in inflamed corneas was determined on days 7 and 16 postinfection in the immunocomplex-treated group of infected mice. Immunocomplex treatment given on days 5, 6, and 7 postinfection significantly increased Foxp3(+) Tregs in draining lymph nodes and in the spleen but failed to reduce the severity of HSK. In terms of the influx of CD4 T cells and granulocytes into inflamed corneas, no significant differences were noted between both groups of mice on day 16 postinfection. Our findings demonstrate that increasing Foxp3(+) Tregs early but not late postinfection in secondary lymphoid tissues is more efficacious in controlling the severity of HSK.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Cell Movement / immunology
  • Cornea / immunology*
  • Cornea / pathology
  • Cornea / virology
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Granulocytes / immunology
  • Herpesvirus 1, Human / immunology*
  • Immunotherapy
  • Interferon-gamma / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / therapeutic use*
  • Keratitis, Herpetic / pathology
  • Keratitis, Herpetic / therapy*
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Viral Load / immunology


  • Antibodies, Monoclonal
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2
  • Interferon-gamma