Characteristics of T cells involved in the expression of delayed hypersensitivity and tumor rejection immunity to 13762A rat mammary adenocarcinoma.
The 13762A rat mammary adenocarcinoma is poorly immunogenic and metastasizes with high frequency to regional lymph nodes and lungs. Tumor rejection immunity (TRI) may be readily transferred with oil-induced peritoneal exudate cells (PEC) from immune rats but the transfer of delayed hypersensitivity (DH) was less reliable. The purposes of the present study were: (1) to compare the optimum conditions for transfer of DH and TRI; (2) to determine whether the TRI effectors were derived from cells which recently divided in the donor; (3) to determine the relative sensitivity of DH and TRI effectors to treatment with radiation and mitomycin C; and (4) to identify the phenotypes of the T-cell subsets responsible for transfer of DH and TRI. The results indicate that transfer of DH requires more cells or a longer interval between transfer and challenge than did TRI. Treatment of the donor with vinblastine (VBL) or hydroxyurea (HU) continuously for 5 days prior to harvest of PEC impairs effectiveness of transferred DH and TRI. This indicates that the effectors proliferated during the period before harvest of the PEC. Treatment of the PEC in vitro with mitomycin C or gamma-radiation eliminates transfer of DH and TRI, but DH is more radiosensitive than TRI. T-cell subsets were identified with the monoclonal antibodies W3/13 (pan-T), W3/25 (helpers), and OX8 (cytotoxic/suppressors). The TRI effectors are nonadherent and express W3/13, W3/25, or OX8 antigens. The, DH effectors are also nonadherent but expressed only W3/13 or W3/25 antigens. Thus, DH systemic adoptive transfer requires more cells or a shorter interval between transfer and challenge than TRI. Both DH and TRI effectors replicate in the donors prior to transfer. The DH effectors are helper T cells but TRI effectors include cells with helper or cytotoxic T-cell marker antigens. We conclude that TRI and DH are probably functions of two T-cell subsets which differed in radiation sensitivity and membrane phenotype. CY pretreatment of the recipients of immune PEC potentiate TRI. The potentiated effects are reduced if the recipients are given nonadherent spleen cells. The responsible cells expressed W3/13 and W3/25 antigens. Thus, CY potentiation is attributed to the depletion of precursors of suppressor T cells.
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D006918:Hydroxyurea / Q000494:pharmacology; D006968:Hypersensitivity, Delayed; D007116:Immunization, Passive; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014747:Vinblastine / Q000494:pharmacology
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D008937:Mitomycins; D016685:Mitomycin; D014747:Vinblastine; D003520:Cyclophosphamide; D006918:Hydroxyurea