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 ex travascular lymphocyte infiltration. To examine the dynamic changes that ar e induced in local lymphocyte migration through regional lymph nodes follow ing TNF-alpha injection, we used a protocol of direct lymphatic cannulation to quantitatively and qualitatively examine the traffic of lymphocytes thr ough regional lymph nodes. We observed that local TNF-alpha injection reduc ed the output of lym phocytes from lymph nodes up to 90 % within 6-10 h fol lowing stimulation. TNF-alpha also altered the specificity of migration of lymphocyte traffic through subcutaneous lymph nodes. In addition to the dec reased output, phenotypic analysis demonstrated decreases in the concentrat ion of gamma delta T cells by up to 30 % following TNF-alpha injection. His tological examination showed that the gamma delta T cells were found in clo se association with VCAM-1-expressing cells in TNF-stimulated lymph nodes, at least some of which appeared to be lymphatic endothelium. These data ind icate that TNF-alpha is capable of altering the number and specificity of l ymphocytes recirculating through stimulated lymph nodes by selectively alte ring the entry of lymphocytes into the efferent lymphatics of inflamed lymp h nodes in vivo.