T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice.
C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to study immunologic responsiveness to the human MUC1 tumor-associated antigen. In the present studies, MUC1.Tg mice were immunized with purified human MUC1 antigen and irradiated MUC1-positive (MC38/MUC1) tumor cells. Immunization with MUC1 antigen was associated with induction of an anti-MUC1 antibody response and no detectable cytotoxic T cell reactivity. Similar findings were obtained after immunization with irradiated MC38/MUC1 tumor cells. The results also demonstrate that immunization of MUC1.Tg mice with MUC1 is associated with decreased levels of CD8+ T cells. In addition, expression of alphabeta T cell receptors and CD28 were down-regulated on CD8+ T cells as a consequence of MUC1 immunization. These findings support a role for T cell suppression in tolerance to MUC1 antigen in MUC1.Tg mice.
Chen
D
D
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Koido
S
S
Li
Y
Y
Gendler
S
S
Gong
J
J
D000818:Animals; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000276:immunology*; D018121:Receptors, Cytokine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D018396:Mucin-1; D018121:Receptors, Cytokine