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.
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.
Cheng
Laurence E
LE
Department of Immunology, University of Washington, Seattle 98195, USA.
Greenberg
Philip D
PD
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000502:physiology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D019898:Autocrine Communication / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006825:Hybridomas; D007156:Immunologic Memory / Q000235:genetics; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D014764:Viral Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015375:Receptors, Interleukin-2; D014764:Viral Proteins; C115679:glycoprotein peptide, Lymphocytic choriomeningitis virus; D016178:Granulocyte-Macrophage Colony-Stimulating Factor