Suppression of antigen- and mitogen-induced proliferation of bovine lymphocytes by excretory-secretory products of Oesophagostomum radiatum.

Excretory-secretory products (ESP) isolated from in vitro-grown stage-3 to -4 larvae of Oesophagostomum radiatum were found to inhibit both the in vitro antigen-specific proliferation of keyhole limpet hemocyanin- and ovalbumin-primed lymphocytes and the proliferation induced by the T-cell mitogen concanavalin A. As little as 50 ng of ESP protein per culture resulted in 50% reductions of subsequent proliferative responses. Antigen-induced responses were 100 to 1,000 times more sensitive to inhibition than were mitogen-induced responses. The inhibitory activity was found to affect the induction of proliferation as evidenced by the observation that complete inhibition was seen when ESP were added to cultures within the first 24 h. ESP were found to have no inhibitory activity when added 72 h after the initiation of the cultures. The inhibition was not a result of a direct action upon macrophages because pulsing of adherent cells with ESP had no more effect on a subsequent proliferative response than did a pulsing of the culture vessel itself. The inhibitory activity eluted from high-pressure liquid chromatography columns in the same fractions as protein standards with molecular weights of 25,000 to 35,000. Of special interest is the fact that this inhibitor of the expansion of immunoreactive clones of lymphocytes is found associated with the stages of parasites most intimately associated with host tissues, namely larval stages 3 and 4.