INVITRO INVASIVENESS OF CTL CLONES AND INVIVO DISSEMINATION OF CTL HYBRIDOMAS

Activated spleen T cells are invasive in hepatocyte and fibroblast cul tures, and this property is dominantly expressed in T cell hybridomas. The invasive potential of the hybrids correlates with their capacity to disseminate in vivo. We have used this model to study the invasive and migratory properties of cytotoxic T lymphocytes (CTLs). Two murine CTL clones were highly invasive, independent of their state of activa tion. CTL hybridomas, derived from one of the clones, were similarly i nvasive. In vivo, CTL hybridoma cells disseminated to extravascular si tes in the liver, kidneys, lungs, ovaria, tubae, uterus, and lymphoid, mesenchymal, and fat tissues. Within 7 to 14 days, 10(6) Cells were l ethal in 100 % of mice. The adhesion molecules CD2, CD8, CD54, L-selec tin, and CD49d (VLA-4 and LPAM-1 alpha-chain) were not expressed by al l CTL hybridomas and therefore not indispensable for invasion in vitro and dissemination in vivo. In contrast, LFA-1 (CD11a/CD18), CD44, and VLA-6 (CD49f/CD29) were expressed on all hybrids. LFA-1 antibodies in hibited CTL hybridoma invasion in vitro, but antibodies inhibiting CD4 4-hyaluronate and VLA-6-laminin interaction had no effect. These resul ts suggest that migration of cytotoxic T cells into noninflamed tissue s is independent of their activation state and does not require L-sele ctin, LPAM-1, CD2, and VLA-4.