Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation

J Immunol. 2009 Feb 1;182(3):1429-38. doi: 10.4049/jimmunol.182.3.1429.

Abstract

T cell proliferation and survival are regulated by the cytokine receptor common gamma-chain-associated cytokines IL-2, IL-7, and IL-15, while IL-4, another gamma-chain-associated cytokine, is thought to primarily affect T cell quality rather than quantity. In contrast, our experiments reveal that endogenously produced IL-4 is a direct, nonredundant, and potent stimulator of CD8(+) T cell proliferation in Ag- and pathogen-induced CD8(+) T cell responses. These stimulatory effects of IL-4 are observed in both BALB/c and C57BL/6 mice and activate both naive and memory/activated phenotype CD8(+) T cells, although the former are stimulated less than are the latter. IL-4 effects are IL-7- and IL-15-independent, but MHC class I-dependent stimulation appears to be required for the mitogenic effect of IL-4 on naive phenotype CD8(+) T cells. Thus, endogenously produced IL-4 is an important regulator of quantitative as well as qualitative aspects of T cell immunity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / administration & dosage
  • Antigens, Dermatophagoides / immunology
  • Bystander Effect / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Death / immunology
  • Cell Proliferation*
  • Cell Survival / immunology
  • Cells, Cultured
  • Female
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / deficiency
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / deficiency
  • Interleukin-4 / genetics
  • Interleukin-4 / physiology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, SCID
  • Mice, Transgenic
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology

Substances

  • Antigens, Dermatophagoides
  • Growth Inhibitors
  • Recombinant Proteins
  • Interleukin-4