Characterization of CC‐chemokine receptor 7 expression on murine T cells in lymphoid tissues

Abstract

Summary Expression of the lymph node homing and CC‐chemokine receptor 7 (CCR7), with L‐selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 and used this antibody to study CCR7 expression on murine T‐cell subsets. Using flow cytometric staining of T cells for visualisation expression of CCR7 in association with CD62L and CD44, a major population of CD4 or CD8 T cells expressing CCR7 were found to be CD62Lhigh CD44low, which would suggest a naïve cell phenotype. By analogy with human studies, memory cells could be subdivided into CCR7high CD62Lhigh CD44high (central memory) and CCR7low CD62Llow CD44high (effector memory). The proportions of these populations were different in lymph node, blood and spleen. Functional, short‐term in vitro polyclonal stimulation of blood, spleen and lymph node cells from naive mice demonstrated that CCR7high CD4 T cells produced predominantly interleukin (IL)‐2, whereas CCR7low CD4 T cells produced both IL‐2 and interferon‐γ (IFN‐γ). However, in contrast to previously published reports, the CCR7high CD8 T‐cell subpopulation produced both IFN‐γ and IL‐2. Analysis of effector T cells, induced by immunization in vivo, showed that a proportion of activated naïve CD4 T cells down‐regulated CCR7 only after multiple cell divisions, and this coincided with the down‐regulation of CD62L and production of IL‐4 and IFN‐γ. Finally, analysis of effector T cells during the phase of maximal clonal expansion of secondary immune responses in vivo indicated that the vast majority of both IL‐2‐ and IFN‐γ‐producing cells are CCR7low, while few cytokine‐expressing CCR7high T cells were detected. Our results support the hypothesis, developed from studies with human cells, that CCR7 may separate functionally different murine memory T‐cell subpopulations, but indicate additional complexity in that CCR7high CD8 T cells also may produce IFN‐γ.

Impact of CCR7 on the gastrointestinal field effect

“…CCR7 Ϫ/Ϫ T cells are effector T cells in the peripheral tissue, e.g., T memory cells, cytotoxic CD8 T cells, regulatory T cells (7,28,31,34). Our previous report that T helper type 1 memory cells activated by dendritic cells in the manipulated intestinal muscularis induce the macrophage activation in the manipulated jejunum as well as in the unmanipulated colon by a CCR9-depdendent migration to unmanipulated gastrointestinal parts support our finding in this study (20).…”

“…ϩ/ϩ dendritic cells are thought to migrate to draining lymph nodes after activation (10,18,25,30,44,46,52,53,60,64,85) to activate and react with T cells (7,17,19,28,31,34,51,58,74,75), which then enter peripheral tissues to perform immune effector functions (5,17,19,29,31,34,53,73,90,91). CCR7 ϩ/ϩ dendritic cells can be found in the peripheral tissue.…”

“…ϩ/ϩ T cells can only be isolated from lymphoid tissue, but not from peripheral tissue (7). CCR7 Ϫ/Ϫ T cells are effector T cells in the peripheral tissue, e.g., T memory cells, cytotoxic CD8 T cells, regulatory T cells (7,28,31,34).…”

“…An important chemokine receptor for the migration and interaction of dendritic cells and T cells in peripheral tissue and secondary lymphoid tissues is CCR7. CCR7 is a member of the G protein-coupled receptor family (7). This receptor is expressed in various lymphoid tissues, on dendritic cells and T cells.…”

Properties of murine CD8+CD27- T cells

“…Based on the presence or absence of both the chemokine receptor CCR7 as well as CD62L, central memory T cells (T CM ) and effector memory T cells (T EM ) have been classified in both mouse and man [7][8][9]. CCR7 binds CCL19 and CCL21, chemokines involved in the attraction of immune cells to lymph nodes while CD62L interacts with a heterogeneous set of glycan-based structures termed peripheral-node addressins, expressed on lymph nodes high endothelial venules.…”