2 research outputs found
Defective Chemokine Production in T-Leukemia Cell Lines and its Possible Functional Role
Peripheral blood lymphocytes and T-cell clones produced nanogram quantities of the chemokines
RANTES, MIP-lα, MIP-lβ, MCP-l, IL-8 and GRO-α as well as the motogenic
cytokine HGF. In contrast, various T-leukemia cell lines at different stages of differentiation
did not produce the same chemokines/cytokines. In order to study the possible functional
importance of the poor chemokine production different T-cell lines were compared with
respect to development of motile forms and migration on extracellular matrix components in
the absence and presence of various chemokines. RANTES, MIP-1α, MIP-1β, IL-8, GRO-α
and lymphotactin did not augment the development of motile forms including the size and
appearance of the pseudopodia activity of the T-leukemia cell lines. The T-cell lines migrated
spontaneously on/to fibronectin in a Boyden chamber assay system. Chemokines augmented
the migration of the T-leukemia cell lines on fibronectin in the Boyden system in a chemotactic
fashion with peak responses at 10 to 50 ng/ml. Thus, the production of chemokines is
defective, in neoplastic T-lymphocytes. The defective chemokine production does not seem to
play any major role for the basic locomotor capacity of the cells but may modulate the
responsiveness to exogenous chemokines
Migration on extracellular matrix surface and infiltration into matrix - two distinguishable activities of human T cells
Migration of T-lymphocytes on a surface coated with extracellular matrix (ECM) components (two-dimensional (2-D) migration) and migration (infiltration) into a matrix (Three-dimesional (3-D) migration) are complex events and the underlying mechanisms are not yet fully understood. Here 2-D and 3-D migration were studied by use of seven leukemic T-cell lines representing discrete differentiation stages, a non-leukemic T-cell clone, and normal peripheral blood T cells. peripheral blood lymphocytes and the T-cell clone produced nanogram quantities of various chemokines, as compared to a production of ≤ 0.05 ng/ml by the T leukemia cell lines. In a Boyden chamber system, the leukemic T-cell lines showed haptotactic migration on fibronectin. The migration was augmented bu exposure to chemokines, including RANTES, MIP-1α, MIP-1β, and IL-8. The T-cell lines showed a peak response at a chemokine concentration of 10-50 ng/ml, whereas the T-cell clone responded optimally at 100 ng/ml. In contrast to a general capability of T-cells to migrate on 2-D ECM, only some of the T-cell lines were capable of 3-D migration into Matrigel or a collagen matrix. The infiltrative capacity was unrelated to the capacity to migrate on or adhere to the substrata. T-cell lines with a capacity to infiltrate produced matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), whereas non-infiltrating cell lines did not produce MMP-9. T-cell lines capable of infiltrating Matrigel or collagen responded to chemokines exposure with increased infiltration, but the chemokines did not render non-infiltrative cell lines infiltrative. Stimulation of infiltration of T-cell lines into collagen by the chemokine SDF-1α was inhibited by somatostatin, a neuropeptide with immunosuppressive properties. In conclusion, the ability to migrate on 2-D substrata and to infiltrate into 3.D substrata was found to be distinguishable properties of T cells. failure of some T-cell lines to infiltrate correlated with the lack of expression of MMP-9. Chemokines stimulated infiltration of infiltrative T-cell lines into collagen and Matrigel but did not render non-infiltrative T-cell lines infiltrative. Finally, a possible physiological mechanism for modulation of the chemokine-stimulated 3-D migration was demonstrated