Influence of mammary tumor progression on phenotype and function of spleen and in situ lymphocytes in mice.
Peripheral immunity to an immunogenic chemically induced mouse mammary adenocarcinoma has been demonstrated in the syngeneic host, i.e., BALB/c mice, by several in vivo and in vitro cell-mediated immune assays. Analysis of the responsiveness of the immune cells within the in situ population may prove to be more indicative of the actual interactions between host and tumors. A centrifugal elutriation procedure was used to isolate tumor-infiltrating lymphocytes. A fluorescence-activated cell sorter revealed that most in situ cells were of the T-cell lineage as determined by the absence of surface immunoglobulin (sIg) and the presence of the Thy 1.2 antigen on their surfaces, while in mice with large tumors there were 27.4% Thy 1.2+ and 47.9% sIg+ cells Further studies using fluorescein-conjugated monoclonal anti-Lyt 1 or anti-Lyt 2 antibodies revealed a decrease in the levels of Lyt 1+ cells and an increase in the percentage of Lyt 2+ lymphocytes in the spleens of mice bearing large tumors. Within the Thy 1.2+ population infiltrating mammary tumors, the proportion of lymphocytes presenting the Lyt 1 marker was decreased in comparison to that of spleens of normal mice (0.58 vs. 0.83). At the same time the relative proportions of Lyt 2+ cells within the Thy 1.2+ population was increased in the in situ population (0.50) compared to those of spleens of normal mice (0.28). Examination of the functional abilities of the in situ lymphocytes (ISL) revealed that ISL derived from small tumors responded to the T-cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A), although at lower levels than those of the splenocytes of the animals from which they were obtained. Responses to PHA were lost rapidly in ISL from large tumors, whereas Con A responses were more durable. In contrast to the spleen cells of tumor bearers, ISL failed to respond to tumor-associated antigens (TAA) at any stage of the disease. The changes in the subsets of T-cells in the spleens of tumor-bearing mice and in ISL may provide an explanation for the decreased activation of ISL by mitogens and for the lack of responsiveness to TAA observed in the splenocytes of mice with large tumors and in the ISL isolated from the mammary adenocarcinomas.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D004261:DNA Replication; D005260:Female; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D013154:Spleen / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D007136:Immunoglobulins