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| Item Type: | Article |
|---|---|
| Title: | Impact of CCR7 on priming and distribution of antiviral effector and memory CTL |
| Creators Name: | Junt, T., Scandella, E., Foerster, R., Krebs, P., Krautwald, S., Lipp, M., 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 |
| 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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