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

Item Type:Article
Title:Impact of CCR7 on priming and distribution of antiviral effector and memory CTL
Creators Name:Junt, T. and Scandella, E. and Foerster, R. and Krebs, P. and Krautwald, S. and Lipp, M. and Hengartner, H. and Ludewig, B.
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.
Keywords:Adoptive Transfer, Cell Movement, Chemokine Receptors, Clonal Deletion, Cytotoxic T-Lymphocytes, Dendritic Cells, Immunologic Cytotoxicity, Immunologic Memory, Inbred C57BL Mice, Kinetics, Knockout Mice, L-Selectin, Lymphocyte Activation, Lymphocytic Choriomeningitis, Lymphocytic Choriomeningitis Virus, Lymphoid Tissue, Organ Specificity, Regulatory T-Lymphocytes, Secondary Immunization, Transgenic Mice, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:173
Number:11
Page Range:6684-6693
Date:1 January 2004
Official Publication:http://www.jimmunol.org/cgi/content/abstract/173/11/6684
PubMed:View item in PubMed

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