Epidermal cell presentation of tumor-associated antigens for induction of tolerance.

Abstract

Intravenous administration of hapten-coupled epidermal cells (EC) induces tolerance in mice. To assess the relevance of this observation to cutaneous tumors, the ability of EC to induce tolerance to the S1509a spindle cell tumor (H-2a) was examined. ECs were prepared from CAF1 (H-2a/d) mice and the supernatant from a freeze-thaw lysate of S1509a cells was used as a source of soluble tumor-associated Ag (TAA). ECs were incubated in TAA or medium alone followed by washing. Two hundred thousand TAA-pulsed ECs, non-TAA-pulsed ECs, or TAA-pulsed ECs killed by freeze-thawing were injected i.v. into groups of CAF1 mice. To determine whether this regimen induced tolerance, a tumor-specific delayed-type hypersensitivity (DTH) response was measured in mice subsequently immunized to the S1509a tumor. To assess the degree of immunity induced in these animals, ECs were prepared and deleted of Thy-1-bearing cells by Ab and complement-mediated lysis. These cells were then pulsed with TAA and 5 x 10(5) were injected into the right hind footpad of each mouse. Footpad swelling was assessed at 24 to 48 h as a measure of the DTH. Mice primed i.v. with viable TAA-pulsed EC but not killed TAA-pulsed EC demonstrated a greatly suppressed DTH response. Other experiments demonstrated that exposure of EC to a dose of ultraviolet radiation (200 J/m2), which inhibits the ability of these cells to induce immunity by subcutaneous injection either before or after TAA pulsing, did not prevent induction of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)