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
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / physiology
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Animals
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Antigens, Viral / immunology
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Autocrine Communication / genetics
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Autocrine Communication / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / virology*
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Cell Division / genetics
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Cell Division / immunology
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Epitopes, T-Lymphocyte / immunology
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Glycoproteins / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Hybridomas
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Immunologic Memory* / genetics
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Lymphocyte Count
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Lymphocytic Choriomeningitis / genetics
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / pathology
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Lymphocytic choriomeningitis virus / immunology*
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology
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Lymphoid Tissue / virology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, Interleukin-2 / biosynthesis
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Receptors, Interleukin-2 / genetics
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Receptors, Interleukin-2 / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Splenomegaly / genetics
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Splenomegaly / immunology
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Splenomegaly / virology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / virology*
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Viral Proteins / immunology
Substances
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Adjuvants, Immunologic
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Antigens, Viral
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Epitopes, T-Lymphocyte
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Glycoproteins
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Receptors, Interleukin-2
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Viral Proteins
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glycoprotein peptide, Lymphocytic choriomeningitis virus
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Granulocyte-Macrophage Colony-Stimulating Factor