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J. Exp. Med.,
Volume 189, Number 9, May 3, 1999 1437-1442
By
From the Center for Immunotherapy of Cancer and Infectious Diseases (MC1601), University of
Connecticut School of Medicine, Farmington, Connecticut 06030-1601
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.
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