4.6 Article

Dendritic cell immunization route determines integrin expression and lymphoid and nonlymphoid tissue distribution of CD8 T cells

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JOURNAL OF IMMUNOLOGY
卷 178, 期 3, 页码 1512-1522

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AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.3.1512

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资金

  1. NCI NIH HHS [R01 CA078400, CA78400] Funding Source: Medline
  2. NIAID NIH HHS [R01 AI068836, R01 AI020963, R37 AI020963, AI059996, T32 AI007496, R21 AI059996, AI20963] Funding Source: Medline
  3. NIGMS NIH HHS [GM07627, T32 GM007267] Funding Source: Medline

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Exogenous dendritic cells (bone marrow-derived dendritic cell (BMDC)) display restricted trafficking in vivo after injection into mice, but the route(s) by which they generate gut-homing effector cells is unclear. Mesenteric lymph nodes (LN) and spleen were differentially targeted by i.p. and i.v. administration of BMDC, respectively, whereas mediastinal LN were targeted by both routes. BMDC injected by either route activated CD8(+) T cells to up-regulate both alpha,beta, and alpha,beta, integrins. However, the lymphoid compartment in which activation occurred determined their expression kinetics, magnitude, and population distribution. Only T cells activated in mesenteric LN after i.p. immunization expressed high levels of alpha(4)beta(7), which also correlated with localization to small intestine. These alpha(4)beta(high)(7) cells also redistributed to mediastinal LN in a manner sensitive to treatment with alpha(4)beta(7) blocking Abs, but not to mucosal addressin cell adhesion molecule-1 blocking Abs. Our results demonstrate the importance of lymphoid compartment, as dictated by immunization route, in determining integrin expression on activated T cells and their distribution in lymphoid and nonlymphoid tissues.

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