Impact of CCR7 on priming and distribution of antiviral effector and memory CTL

J Immunol. 2004 Dec 1;173(11):6684-93. doi: 10.4049/jimmunol.173.11.6684.

Abstract

The chemokine receptor CCR7 is a key factor in the coordinate migration of T cells and dendritic cells (DC) into and their localization within secondary lymphoid organs. In this study we investigated the impact of CCR7 on CD8(+) T cell responses by infecting CCR7(-/-) mice with lymphocytic choriomeningitis virus (LCMV). We found that the absence of CCR7 affects the magnitude of an antiviral CTL response during the acute phase, with reduced numbers of virus-specific CTL in all lymphoid and nonlymphoid organs tested. On the single cell level, CCR7-deficient CTL gained full effector function, such that antiviral protection in CCR7-deficient mice was complete, but delayed. Similarly, adoptive transfer experiments using DC from CCR7-deficient or competent mice for the priming of CCR7-positive or CCR7-negative CD8(+) T cells, respectively, revealed that ectopic positioning of DC and CTL outside organized T cell zones results in reduced priming efficacy. In the memory phase, CCR7-deficient mice maintained a stable LCMV-specific CTL population, predominantly in nonlymphoid organs, and rapidly mounted protective CTL responses against a challenge infection with a vaccinia virus recombinant for the gp33 epitope of LCMV. Taken together, the CCR7-dependent organization of the T cell zone does not appear to be a prerequisite for antiviral effector CTL differentiation and the sustenance of antiviral memory responses in lymphoid or peripheral tissues.

Publication types

  • Comparative Study

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Clonal Deletion / genetics
  • Cytotoxicity, Immunologic* / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Immunization, Secondary
  • Immunologic Memory* / genetics
  • Kinetics
  • L-Selectin / biosynthesis
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / prevention & control
  • Lymphocytic choriomeningitis virus / immunology*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / pathology
  • Lymphoid Tissue / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Receptors, CCR7
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / deficiency
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / physiology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / transplantation
  • T-Lymphocytes, Cytotoxic / virology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / virology

Substances

  • Ccr7 protein, mouse
  • Receptors, CCR7
  • Receptors, Chemokine
  • L-Selectin