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Abstract

The Arkansas Rous Sarcoma Regressor (AR) and Progressor (AP) lines of chickens represent an excellent model to study immune responses to tumors. Both lines of chickens initially develop tumors when injected with Rous sarcoma viros (RSV) or with DNA coding for the RSV oncogene v-src (v-src DNA). AR chickens will eventually regress the tumors whereas AP chickens will allow the tumors to progress to a terminal stage. By using both v-src DNA and RSV for tumor induction, we were able to compare the immune response to tumor antigens alone and tumor antigens in combination with viral components, respectively. To study the ability of v-src DNA to induce tumors in AR and AP chickens, 3-day-old AR and AP chicks were injected with v-src DNA, and the incidence and development of tumors was monitored. To gain insight into the role of lymphocytes in tumor regression, 9-week-old AR and AP chickens were injected into the wing web with either PBS (vehicle control), vsrc DNA in PBS, or RSV in PBS. Blood was collected prior to injection and during tumor development. Tumors were collected when present. Lymphocyte profiles in blood and tumors were determined by immunofluorescent staining with a panel of antibodies and flow cytometry. Based on tumor induction data, the level of the chicken's immunocompetence is important, not only in the ability to regress tumors, but also in the susceptibility to tumor induction by v-src DNA. Cell population analyses of tumor-infiltrating lymphocytes (TIL) revealed the presence of different types and proportions of immune cells in DNA and RSV induced regressing and progressing tumors. DNA induced tumors were shown to display higher levels of regulatory T cells (CD4+) and a higher ratio of CD4+ to CDS+ TIL than RSV induced tumors, indicating a different response occurs to tumor antigens alone versus tumor plus viral antigens. Additionally, the percentage of CD4+CD8+ TIL. a cell type usually not found in the periphery and whose function is unknown, was higher in AR tumors than AP tumors. Of particular interest was the discovery of CD8a-b+ TIL This cell type has been recently characterized using transgenic human cells, and appears to be an ineffective cytotoxic T cell subtype. The elevated proportions of this novel cell type in progressing tumors may contribute to the ineffective immune response in AP compared to AR birds.

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