IMMUNOSURVEILLANCE MODELED IN-VITRO - NAIVE AND MEMORY T-CELLS SPONTANEOUSLY MIGRATE ACROSS UNSTIMULATED MICROVASCULAR ENDOTHELIUM

As a model for T cell immigration into non-lymphoid tissue we set up a n in vitro assay that would allow us to investigate the phenotype of T lymphocytes from peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) or peripheral blood (PBL) of mice, which were able to spontaneo usly migrate across unstimulated microvascular endothelium. The transe ndothelial migrating T cell population was enriched for T lymphocytes expressing a 'recently activated/ memory' phenotype: LFA-1/CD44/1CAM-1 (high), but also contained CD45RB(high) and LFA-1(low) T cells, which in the case of MLN T cells were phenotyped as CD4(+) and thus characte rized as naive T cells, Transmigrated T cells could be further disting uished from their original populations and from each other by their di stinct but heterogeneous expression patterns for L-selectin, alpha 4 b eta 7-integrin and PECAM-1. This observation suggests the presence of phenotypically different migratory T cells among MLN, PLN and PBL. Add itional studies provided evidence that the capacity to migrate across unstimulated microvascular endothelium was a characteristic of a T cel l population that could phenotypically be differentiated from activate d T cells, The endothelial cells were found to play an active role in selecting the traversing T cell population, as they controlled the num ber and phenotype of spontaneously transmigrating T cells, Our studies suggest that the capacity to transmigrate across unstimulated microva scular endothelium and hence to immigrate into nonlymphoid tissue is o wned by a phenotypically heterogeneous T cell population, which is enr iched for memory T cells but not devoid of naive T cells.