A role for lymphatic endothelium in the sequestration of recirculating γ δ T cells in TNF‐α‐stimulated lymph nodes

TNF-α 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-α 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-α injection reduced the output of lymphocytes from lymph nodes up to 90 % within 6 – 10 h following stimulation. TNF-α 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 γ δ T cells by up to 30 % following TNF-α injection. Histological examination showed that the γ δ 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-α 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.