l‐selectin expression on thymic emigrants defines two distinct tissue‐migration pathways

Abstract

SUMMARYWe have studied the appearance and phenotype of recent thymic emigrants in blood, spleen and lymph nodes (LN) of neonatal lambs. Using in situ labelling of thymocytes with¯uoroscein isothiocyanate (FITC), we examined the expression of the LN homing receptor L-selectin on ab and cd subsets of recent thymic emigrants 24 hr after labelling. There were marked differences in the proportions of CD4 + , CD8 + and cd T-cell receptor (TCR + ) cells exported from the thymus to spleen compared to lymph nodes. Spleen was enriched in CD8 + and cd TCR + emigrants while LN were enriched in CD4 + emigrants. There were also marked differences in the expression of L-selectin by emigrants homing to spleen compared with those homing to lymph nodes. While the majority of thymic emigrants in LN expressed L-selectin, considerably fewer emigrants in spleen wereThe presence of large numbers of CD8 + L-selectin ± and cd TCR + L-selectin ± thymic emigrants homing to spleen raises the possibility that unique homing receptor speci®cities underpin the migration of T cells to spleen as distinct from lymph nodes.

A CXCR4-Dependent Chemorepellent Signal Contributes to the Emigration of Mature Single-Positive CD4 Cells from the Fetal Thymus

“…This may be of particular relevance as we found two different subpopulations of SP CD8 emigrants, one expressing CD62L low and the other CD62L high . It has been previously reported that two main subpopulations of SP CD8 thymic emigrants exist, each expressing different levels of L-selectin and characterized by a different homing commitment (32,33). In addition, our data show that DP thymocytes are able to emigrate from fetal thymi at early but not at late-stage culture.…”

Recent Thymic Emigrants (CD4+) Continuously Migrate Through Lymphoid Organs: within the Tissue They Alter Surface Molecule Expression

“…However, only the CD44 molecule met this expectation [47]: 60% of the cells were positive for CD44 among RTE, about 80% among naive T cells, and nearly 100% among memory T cells. As in mice [25, 48] and sheep [49], most of the CD4 + RTE in rat are l ‐selectin positive and ICAM‐1 negative, an expression pattern comparable to that of naive CD4 + T cells. Surprisingly, the expressions of α 4 ‐integrin, LFA‐1, and IL2R on RTE are different from the expression of naive T cells, and closely resembles that of memory T cells.…”

Cell death and thymic export during fetal life

“…We have shown previously in neonatal lambs that there are two separate populations of thymic emigrants which display distinct tissue-specific homing pathways to spleen and LN [41]. The overwhelming majority of the spleen-homing emigrants were CD8 + L-selectin -T cells, whereas the LN-homing emigrants were predominantly CD4 + T cells which did express Lselectin [42]. It seems very unlikely that thymic emigrants migrated randomly to the fetal spleen and were then selectively retained, because the migration of emigrants to the spleen occurred with such exquisite specificity.…”

“…Peripheral tissue suspensions were prepared and stained as previously described [42]. Unlabeled thymocytes were stained using biotinylated anti-CD4 mAb + anti-CD8-FITC or biotinylated anti-TCRcd mAb, followed by streptavidin-allophycocyanin (SA-APC; BD Biosciences).…”