Identification of an IL-2 binding protein in the saliva of the lyme disease vector tick, Ixodes scapularis

A potent inhibitor of mitogen-stimulated T cell proliferation exists in the saliva of several species of hard ticks, including the Lyme disease vector tick, Ixodes scapularis. Our characterization of this phenomenon has led t o the identification of a possible mechanism for the T cell inhibitory acti vity of I. scapularis saliva. The T cell inhibitor can overcome stimulation of mouse spleen cells with anti-CD3 mAb; however, a direct and avid intera ction with T cells does not appear to be necessary. Tick saliva inhibits a mouse IL-2 capture ELISA, suggesting that a soluble IL-2 binding factor is present in the saliva. This hypothesis was verified by using a direct bindi ng assay in which plate-immobilized tick saliva was shown to bind both mous e and human IL-2. Elimination of the IL-2 binding capacity of saliva in the in vitro assays by trypsin digestion demonstrated that the IL-2 binding fa ctor is a protein. These experiments comprise the first demonstration of th e existence of such a secreted IL-2 binding protein from any parasite or pa thogen. This arthropod salivary IL-2 binding capacity provides a simple mec hanism for the suppression of T cell proliferation as well as for the activ ity of other immune effector cells that are responsive to IL-2 stimulation. Relevance of the tick T cell inhibitory activity to the human immune syste m is demonstrated by the ability of tick saliva to inhibit proliferation of human T cells and CTLL-2 cells grown in the presence of human IL-2.