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Title: INHIBITION OF BOVINE T LYMPHOCYTE RESPONSES BY PRODUCTS OF THE STOMACH WORM, OSTERTAGIA OSTERTAGI

Author
item GOMEZ-MUNOZ, T - UNIV OF MADRID
item Canals, Ana
item ALMERIA, S - UNIV OF BARCELONA
item Zarlenga, Dante
item Gasbarre, Louis

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: The brown stomach worm, Ostertagia ostertagi is the most economically important parasite of cattle in temperate regions of the world. It has remained a severe problem to cattle raisers in large part because cattle take a prolonged period of time before they become immune to the parasite. This delay in immunity may be the result of the parasite s ability to suppress the bovine immune system. We have found that extracts and secretions of the parasite may suppress the growth of T lymphocytes. T lymphocytes control cellular immunity in the host. This suppression is not due to a direct toxicity of the worm products, but instead involves both the suppression of the production of growth promoters for the immune system, and the enhancement of the secretion of growth inhibitors. This activity appears to be the unique property of a particular larval stage of the parasite, and is not found in other life cycle stages or in other cattle nematodes. These results explain why cattle don t become immune to the parasites, and offer future targets for drug and/or immunological therapies.

Technical Abstract: In the present study we have employed 3 different life cycle stages of the nematode Ostertagia ostertagi to determine if products of this economically important parasite inhibit in vitro proliferation of Con A-stimulated cells. We have demonstrated an inhibitory effect upon the growth of Con A-stimulated lymphocytes after addition of fourth stage larval (L4) soluble extract to the cultures. Extracts from the third stage larvae (L3) or adult worms had little or no inhibitory activity. The suppressive products were shown to be secreted by the late L4. The L4 extract caused slight but not statistically significant decreases in the percentage of T cells in cultures. Consequently, B cell percentages were increased throughout the culture interval. No changes were seen in ABSLG1tage of cells positive for markers for CD4, CD8, # T cells, or monocytes/macrophages. In contrast, there was a strong and significant reduction in the expression of the IL2 receptor in cells cultured in the presence of the worm extract. The suppressive activity is reversible if the L4 products are removed from culture. There is no immediate effect on proliferating cells and the L4 extract must be in culture for 24-48 hours before suppression is observable. There was no evidence of either necrosis or apoptosis resulting from the presence of L4 products in culture. The expression of messenger RNA for interleukins 2, 4, 13, TNF- alpha, and IFN-gamma was decreased when L4SE was included in cultures of Con A stimulated cells. In contrast, messenger RNA expression of transforming growth factor-beta and interleukin-10 was increased in cells growing in the presence of L4 products.