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Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, AL 36688;
Department of Surgery, University of South Alabama College of Medicine, Mobile, AL 36693; and
Department of Pathology, University of South Alabama College of Medicine, Mobile, AL 36617
Oncofetal Ag (OFA) is a 44-kDa glycoprotein expressed during early
to mid-gestation fetal development and re-expressed as a surface Ag by
tumor cells soon after transformation. The Ag is detectable on all
types of human and rodent tumors tested, but is undetectable on normal
cells. In experimental animals it is autoimmunogenic and induces
potentially protective T cell responses both after experimental
immunization and during tumor development subsequent to carcinogenic
insult. To determine whether this tumor-associated Ag is also
immunogenic for human T lymphocytes, breast carcinoma patients
peripheral blood mononuclear leucocytes were stimulated in vitro with
autologous tumor cells in the presence of IL-2,
-IFN, and IL-6 for 2
wk. The tumor-reactive cells were then restimulated and cloned by
limiting dilution, and the clones were analyzed. We established 24, 19,
11, and 16 tumor-reactive clones from the four respective patients. Of
those, 4, 6, 4, and 7, respectively, proliferated specifically to
purified OFA. Both CD4 and CD8 OFA-specific clones were established,
which responded equally well to purified OFA or 32- to 44-kDa immature
laminin receptor protein. All were CD3+,
TCR-
ß+. All CD4 clones secreted
-IFN, but neither
secreted IL-4 nor IL-10. Both IFN-
-secreting cytotoxic CD8 clones
and IL-10-secreting inhibitory CD8 clones were established. Thus,
during human cancer development, the same types of OFA-specific
effector and regulatory T cells are induced as during murine T
lymphomagenesis.
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