The dual nature of specific immunological activity of tumor-derived gp96 preparations.
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.
Chandawarkar
R Y
RY
Center for Immunotherapy of Cancer and Infectious Diseases (MC1601), University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA.
Wagh
M S
MS
Srivastava
P K
PK
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C052646:sarcoma glycoprotein gp96 rejection antigens