IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells

Deborah M. Brown, Cris Kamperschroer, Allison M. Dilzer, Deborah M. Roberts, Susan L. Swain

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

CD4 T cell effectors can promote survival against lethal influenza virus via perforin mediated cytolytic mechanisms; however, our understanding of how naïve CD4 cells differentiate into class II restricted killers remains obscure. To address this, TCR Tg CD4 cells were activated in vitro and examined for their ability to lyse target cells. We found that cytokine polarized CD4 T cell effectors displayed cytolytic activity with the hierarchy Th0 > Th1 > Th2. Further, IL-4 inhibited the generation of cytotoxic CD4 cells. LPS stimulated B cells and bone marrow derived dendritic cells (BMDC) both induced potent cytolytic activity; however, IL-6, TGF-β, IL-10, IL-12 or TNF-α were not required for inducing cytolytic activity in CD4 effectors. Antigen dose had a marked effect on cytotoxicity: low concentrations of peptide induced more potent cytolytic activity than relatively high concentrations. At low peptide concentration, exogenous IL-2 was necessary to drive granzyme B (GrB) expression and perforin mediated lysis. Thus, low antigen dose and early activation signals via IL-2 direct the CD4 T cell response toward effectors with perforin mediated cytolytic potential. These data have implications for the design of vaccines that may induce cytolytic CD4 cells in vivo and improve cell-mediated immunity to viral and bacterial infections.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalCellular Immunology
Volume257
Issue number1-2
DOIs
StatePublished - Mar 31 2009

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Perforin
CD4 Antigens
Interleukin-2
T-Lymphocytes
Antigens
Peptides
Virus Diseases
Interleukin-12
Orthomyxoviridae
Bacterial Infections
Cellular Immunity
Interleukin-4
Interleukin-10
Dendritic Cells
Interleukin-6
B-Lymphocytes
Vaccines
Bone Marrow
Cytokines

Keywords

  • CD4 subsets
  • Cytotoxicity
  • IL-2
  • Peptide dose
  • Perforin

ASJC Scopus subject areas

  • Immunology

Cite this

IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells. / Brown, Deborah M.; Kamperschroer, Cris; Dilzer, Allison M.; Roberts, Deborah M.; Swain, Susan L.

In: Cellular Immunology, Vol. 257, No. 1-2, 31.03.2009, p. 69-79.

Research output: Contribution to journalArticle

Brown, Deborah M. ; Kamperschroer, Cris ; Dilzer, Allison M. ; Roberts, Deborah M. ; Swain, Susan L. / IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells. In: Cellular Immunology. 2009 ; Vol. 257, No. 1-2. pp. 69-79.
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