Intravital microscopy identifies selectins that regulate T cell traffic into allografts
Thomas R. Jones, … , Thomas C. Pearson, Christian P. Larsen
Thomas R. Jones, … , Thomas C. Pearson, Christian P. Larsen
Published December 1, 2003
Citation Information: J Clin Invest. 2003;112(11):1714-1723. https://doi.org/10.1172/JCI19391.
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Article Immunology

Intravital microscopy identifies selectins that regulate T cell traffic into allografts

Abstract

T cell homing to sites of injury and inflammation is a critical step for adaptive immune responses. While much has been learned regarding T cell homing to lymphoid tissues, few studies have directly observed trafficking events during an effector response. In this study, we developed a model that uses intravital fluorescence videomicroscopy to determine the molecules critical to T cell rolling within skin allograft microvasculature during the effector phase of the rejection response. Additional studies were performed to quantify T cell infiltrates as rejection progressed. We found that P-selectin and E-selectin expressed on postcapillary venules play overlapping roles in the recruitment of activated T cells in a SCID reconstitution model of skin graft rejection and are important in T cell accumulation at the graft site. Surprisingly, we also found that naive T cells are recruited and accumulate via constitutive T cell L-selectin and upregulated L-selectin ligands on rejecting allograft vasculature. These data indicated that a specific retinue of molecules is upregulated during the rejection response, and they suggest potential future therapeutic targets.

Authors

Thomas R. Jones, Nozomu Shirasugi, Andrew B. Adams, Thomas C. Pearson, Christian P. Larsen

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Figure 6

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CD62P and CD62E play overlapping roles in rolling and firm adhesion. CFS...
CD62P and CD62E play overlapping roles in rolling and firm adhesion. CFSE-labeled activated T cells were infused in B6 SCID recipients of BALB/c allografts 4 days after reconstitution with wild-type B6 T cells for IVM experiments. Animals received the indicated treatments. (a) Rolling interactions were significantly inhibited by anti–mouse CD62P (white bars) versus isotype control (black bars). Additional anti-CD62E with anti-CD62P (gray bars) did not significantly reduce rolling from that seen with anti-CD62P alone. *P < 0.002 vs. isotype controls. Data are mean ± SEM; n = 3 in each group. (b) Firm adhesion events were significantly inhibited by anti-CD62P alone. Additional blockade with anti-CD62E further reduced these interactions. †P < 0.04 vs. isotype, ††P < 0.03 vs. anti-CD62P alone and P < 0.007 vs. isotype controls. Data are mean ± SEM; n = 3 in each group. (c) Rolling interactions were not affected by anti-CD62E treatment alone (white bars), compared to isotype control (black bars). Additional anti-CD62P (gray bars) reduced rolling to the levels observed in a. **P < 0.02 vs. anti-CD62E alone. Data are mean ± SEM; n = 3 in each group. (d) Anti-CD62E alone significantly inhibited firm adhesion interactions relative to isotype controls. Additional anti-CD62P further reduced these interactions. #P < 0.02 vs. isotype control, ##P < 0.008 vs. anti-CD62E alone. Data are mean ± SEM; n = 3 in each group.