Figure 8.
Summary of the effects of S1P1 deficiency or FTY720 treatment on the trafficking of adoptively transferred lymphocytes. The effects of S1P1 deficiency and FTY720 treatment on cell entry or cell exit to various lymphoid organs are presented for T cells (top) and B cells (bottom). Conclusions on “cell entry” are derived from our short-term homing and IVM experiments, whereas “cell exit” summarizes our findings in emigration experiments, as well as observations made by others. “Cell content in organ” refers to our results in long-term (16 to 20 hours) homing experiments and provides a measure of the cell numbers of adoptively transferred cells found in a particular organ. Open arrows within the organ drawings symbolize the entry and exit routes of naive lymphocytes for each organ. Other symbols and abbreviations are explained as follows: upward arrows indicate enhancement; downward arrows, reduction; lateral arrows, indicate no effect; and ND, not determined. Arrows in parentheses indicate a pronounced, although not statistically significant, tendency. Footnotes: a, based on the fact that cell exit from PP is reduced; b, occurs independently of T cell–expressed S1P1; c, the profound lymphopenia in blood suggests a reduction in lymphocyte exit from spleen; d, although not addressed experimentally, it remains possible that T-cell accumulation in BM is increased not only due to enhanced cell entry but also due to decreased cell exit; e, based on the analysis of endogenous single-positive CD4+ or CD8+ T cells in thymus of S1P1–/– chimeras and FTV720-treated mice8,11,15 ; f, suggested by thoracic duct lymph canulation experiments, which have revealed a substantial reduction of S1P1-deficient11 or FTY720-treated T and B cells7 in lymph; g, as shown by Cinamon et al17 ; h, the fact that B-cell entry is unaffected, but S1P1 deficiency or FTY720 treatment leads to accumulation of cells in BM after long-term adoptive transfer, suggests that B-cell exit from BM is reduced.