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Lamina propria T lymphocytes (LPL-T) have a low proliferative potential in vitro. We asked whether LPL-T are also hyporesponsive in vivo and whether this is specific for the alphabeta T cell receptor (TCR). Mitogenic mAb directed at the alphabeta TCR, CD2, CD28, or control mAbs plus IL-2 were injected into rats. Proliferation and/or apoptosis were detected by double staining using 5-bromo-2'-deoxyuridine/TUNEL and the alphabeta TCR. LPL-T were hyporesponsive to various stimuli compared to other T cells. The strongest proliferation was found upon CD2/CD28 stimulation (LPL-T: 281 +/- 6%; spleen: 642 +/- 31%). LPL-T proliferation was only detectable at 24 h while proliferation in other compartments also occurred later. Hyporesponsiveness was not caused by enhanced T cell apoptosis upon alphabeta TCR stimulation. In conclusion, stimulation of LPL-T results in much shorter and weaker in vivo proliferation than in other lymphoid organs. Overall, CD2/CD28 costimulation is the strongest T cell stimulus in vivo.

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