Mice immunized with optimal doses of autologous tumor-derived gp96 resist a challenge with the tumor that was the source of gp96, immunization with quantities of gp96 5-10 times larger than the optimal dose does not elicit tumor immunity. This lack of effect is shown to be an active, antigen- specific effect, in that immunization with high doses of tumor-derived gp96, but not normal tissue-derived gp96, downregulates the antitumor immune response. Furthermore, immunization with fractionated doses of gp96 elicits the same kind and level of response as elicited by a single dose equivalent to the total of the fractionated doses. This is true of the tumor-protective doses as well as the high downregulatory doses of gp96. The downregulatory activity can be adoptively transferred by CD4+ but not CD8+ T lymphocytes from mice immunized with high doses of gp96. These observations indicate that immunization with gp96 induces a highly regulated immune response that, depending upon the conditions of immunization, results in tumor immunity or downregulation.
CITATION STYLE
Chandawarkar, R. Y., Wagh, M. S., & Srivastava, P. K. (1999). The dual nature of specific immunological activity of tumor-derived gp96 preparations. Journal of Experimental Medicine, 189(9), 1437–1442. https://doi.org/10.1084/jem.189.9.1437
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