A role for lymphatic endothelium in the sequestration of recirculating gamma delta T cells in TNF-alpha-stimulated lymph nodes.

TNF-alpha is one of the most potent immunoregulatory molecules in vivo. In addition to important regulatory effects, it is also a potent inducer of extravascular lymphocyte infiltration. To examine the dynamic changes that are induced in local lymphocyte migration through regional lymph nodes following TNF-alpha injection, we used a protocol of direct lymphatic cannulation to quantitatively and qualitatively examine the traffic of lymphocytes through regional lymph nodes. We observed that local TNF-alpha injection reduced the output of lymphocytes from lymph nodes up to 90% within 6-10 h following stimulation. TNF-alpha also altered the specificity of migration of lymphocyte traffic through subcutaneous lymph nodes. In addition to the decreased output, phenotypic analysis demonstrated decreases in the concentration of gamma delta T cells by up to 30% following TNF-alpha injection. Histological examination showed that the gamma delta T cells were found in close association with VCAM-1-expressing cells in TNF-stimulated lymph nodes, at least some of which appeared to be lymphatic endothelium. These data indicate that TNF-alpha is capable of altering the number and specificity of lymphocytes recirculating through stimulated lymph nodes by selectively altering the entry of lymphocytes into the efferent lymphatics of inflamed lymph nodes in vivo.