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

Abstract

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 hemocyaninand 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 initimately associated with host tissues, namely larval stages 3 and 4. Many parasitic infections have been shown to exert strong immunoregulatory effects upon the host. In many cases, this immunoregulation has been shown at the level of either the host immune response to immunization with defined antigens or the response to infection by unrelated infectious agents. Examples of immunoregulation at the systemic level have been demonstrated after infection with a number of parasite species (3,10,16,28). In contrast, little is known about the regulation by parasites at the cellular level of the host immune response. African trypanosomes have been shown to suppress specific antitrypanosome in vitro T-cell responses (18,19). This suppression was found to affect both the T-cell and macrophage components of the response (19), and that responsiveness could be at least partially restored by the addition to the culture of supernatants of activated T cells (20).Oesophagostomum radiatum is a nematode which infects the distal small intestine, cecum, and proximal colon of cattle. After the infective larvae are ingested in contaminated herbage, they penetrate the mucosa of the distal ileum and then undergo a complex development in the submucosa, leading to a marked inflammation at the sites of development. This inflammation results in the formation of large nodules, accounting for the common name of the parasite, the nodular worm of cattle. Recent advances in large-scale in vitro cultivation of 0. radiatum make it possible to obtain relatively synchronous populations of advanced stages from infective larvae through young adults (15). These techniques permit both the iso...

Heligmosomoides polygyrus immunomodulatory factor (IMF), targets T‐lymphocytes

“…Parasitic organisms would appear to perpetuate their survival by employing a range of immunosuppressive strategies (Playfair 1982). For example, they may modulate the immune system by interfering with lymphocyte proliferation (Raybourne, Desowitz, Kliks & Deardoff 1983), causing the death of T lymphocytes (Mazingue, Dessaint, Schmitt-Verhulst, Cerottini & Capron 1983), by depressing IgE responses (Langlet, Mazingue, Dessaint & Capron 1984) reducing B lymphocyte numbers (Cross & Klesius 1989), or by stimulating so called 'suppressor' cell activity (Liew, Scott, Lim & Croft 1987, Price & Turner 1986, Gasbarre, Romanowski & Douvres 1985. Both the induction and expression of immune effector mechanisms can be affected (Pritchard & Behnke 1985).…”

Products of Fourth‐Stage Larvae of Oesophagostomum dentatum Induce Proliferation in Naïve Porcine Mononuclear Cells

“…Homogenates of Ostertagia ostertagi (L 3 , L 4 and adults) displayed no modulating effects on bovine peripheral blood MNC (DeMarez et al., 1997). Gasbarre et al. (1985) demonstrated an inhibitory effect of both L 3 and L 4 of O. radiatum on the bovine lymphoblastogenesis.…”

“…Findings are also hard to generalize, as immune responses (involved cells and mechanisms) depend on the parasite and the infected species (Crook, 1990). Gasbarre et al. (1985), for example, reported an inhibiting effect of third‐ and fourth‐stage larvae of Oesophagostomum radiatum on bovine lymphoblastogenesis.…”

Immunology and Prevention of Infection in Feedlot Cattle

“…94 Substances secreted by nematodes progressing through larval stages have been shown to suppress proliferation of bovine lymphocytes. 36 Therefore, controlling coccidiosis and parasites in feedlot cattle is important for maintaining optimal immune function and resistance to infectious disease.…”