Selective delivery of augmented IL-2 receptor signals to responding CD8+ T cells increases the size of the acute antiviral response and of the resulting memory T cell pool

J Immunol. 2002 Nov 1;169(9):4990-7. doi: 10.4049/jimmunol.169.9.4990.

Abstract

CD8(+) T cells respond to IL-2 produced both endogenously and by CD4(+) Th during an antiviral response. However, IL-2R signals can potentially promote CD8(+) T cell death as well as proliferation, making it unclear whether IL-2R signals provide a predominantly positive or negative effect upon CD8(+) T cell responses to viral infection. To more precisely define the direct role of IL-2R signaling on CD8(+) T cells during the response to a virus, we examined the effect of delivering augmented IL-2R signals selectively to CD8(+) T cells responding to lymphocytic choriomeningitis virus infection. Although naive CD8(+) T cells are competent to produce IL-2, CD8(+) T cells lose this capacity upon differentiation into effector CD8(+) T cells. However, effector CD8(+) T cells do retain the capacity to produce GM-CSF upon Ag stimulation. Thus, to deliver enhanced autocrine IL-2R signals to CD8(+) T cells, we established a transgenic mouse strain expressing a chimeric GM-CSF/IL-2R (GMIL2R). As GM-CSF production is Ag dependent, the GMIL2R delivers an augmented IL-2R signal exclusively to CD8(+) T cells responding to Ag. Following lymphocytic choriomeningitis virus infection, GMIL2R transgenic mice exhibited an increase in both the peak CD8(+) T cell response achieved and the size of the resulting memory pool established. Upon secondary viral challenge, the GMIL2R also enhanced the proliferative response of memory CD8(+) T cells. Thus, our findings indicate that IL-2 delivery to responding CD8(+) T cells is a limiting factor in both the acute and memory antiviral responses.

Publication types

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

MeSH terms

  • Acute Disease
  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / physiology
  • Animals
  • Antigens, Viral / immunology
  • Autocrine Communication / genetics
  • Autocrine Communication / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology*
  • Cell Division / genetics
  • Cell Division / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Glycoproteins / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Hybridomas
  • Immunologic Memory* / genetics
  • Lymphocyte Count
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic choriomeningitis virus / immunology*
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Splenomegaly / genetics
  • Splenomegaly / immunology
  • Splenomegaly / virology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / virology*
  • Viral Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Receptors, Interleukin-2
  • Viral Proteins
  • glycoprotein peptide, Lymphocytic choriomeningitis virus
  • Granulocyte-Macrophage Colony-Stimulating Factor