Interleukin-6R binds to IL6 with low affinity, but does not transduce a signal. A soluble IL-6R is produced by both naive and memory CD4 T cells upon TCR activation. The production of IL6-R by activated CD4 T cells is mediated by shedding of the membrane-bound IL-6R, and this process correlates with the e, Xenopus/Amphibian,pression of the metalloproteinase ADAM17 in these cells. In contrast to CD4 T cells, CD8 T cells do not e, Xenopus/Amphibian,press ADAM17 and their production of IL-6R is negligible. Thus, during an immune response CD4 T cells are an important source of IL-6R. Production of IL-6R by autoreactive CD4 T cells may contribute to their role in the development of autoimmune disease by conferring IL-6-responsiveness to cells lacking IL-6R such as synoviocytes.