Inflammation enhances IL-2 driven differentiation of cytolytic CD4 T cells

Aspen M. Workman, Ashley K. Jacobs, Alexander J. Vogel, Shirley Condon, Deborah M Brown

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing correlated with STAT5 activation and CD25 expression in vitro, suggesting that signaling through the high affinity IL-2R is critical for full cytotoxicity. IL-2 signaling was also necessary in vivo for inducing the Th1 phenotype and IFN-γ expression in CD4 T cells during influenza A (IAV) infection. In addition, GrB expression, as measured by mean fluorescent intensity, was decreased in CD25 deficient cells; however, the frequency of CD4 cells expressing GrB was unchanged. Similarly, analysis of cytolytic markers such as CD107a/b and Eomesodermin indicate high IL-2Rα expression is not necessary to drive the CD4 CTL phenotype during IAV infection. Thus, inflammatory signals induced by viral infection may overcome the need for strong IL-2 signals in driving cytotoxicity in CD4 cells.

Original languageEnglish (US)
Article numbere89010
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 20 2014

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T-cells
interleukin-2
Interleukin-2
T-lymphocytes
inflammation
Cytotoxicity
Inflammation
T-Lymphocytes
Granzymes
cytotoxicity
Perforin
Virus Diseases
Phenotype
phenotype
infection
Interleukin-2 Receptors
receptors
T-Cell Antigen Receptor
Infection
Human Influenza

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Inflammation enhances IL-2 driven differentiation of cytolytic CD4 T cells. / Workman, Aspen M.; Jacobs, Ashley K.; Vogel, Alexander J.; Condon, Shirley; Brown, Deborah M.

In: PloS one, Vol. 9, No. 2, e89010, 20.02.2014.

Research output: Contribution to journalArticle

Workman, Aspen M. ; Jacobs, Ashley K. ; Vogel, Alexander J. ; Condon, Shirley ; Brown, Deborah M. / Inflammation enhances IL-2 driven differentiation of cytolytic CD4 T cells. In: PloS one. 2014 ; Vol. 9, No. 2.
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