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Damselfish with neurofibromatosis exhibit cytotoxicity towards retrovirus infected cells
1University of Miami School of Medicine, Department of Microbiology and Immunology, FL 33101, USA.
Abstract:
Lymphocytes from tumor-bearing damselfish are cytotoxic towards target cell lines derived from damselfish neurofibromatosis. These cell lines contain at least one retrovirus which appears to be related to the etiology of the disease. The current studies were designed to characterize the effectors of this cytotoxic reaction. Data presented here show that cells separated using an antibody (5C6.10.4) directed towards non-specific cytotoxic cells of catfish sequesters all antitumor activity in the 5C6.10.4 negative population. Thus, damselfish 5C6.10.4 positive cells bind to tumor targets, but do not contribute to target cell death. In contrast, 5C6.10.4 positive cells are cytotoxic towards xenogeneic erythrocytes. Cytotoxicity of splenocytes from animals inoculated with virus purified from the 88-503 cell line suggested that prior exposure to the retrovirus enhanced reactivity, especially towards 88-503. In addition, cytotoxicity was significantly greater in tumor homogenate injected animals that resisted tumor development for more than 5 months as compared to those that developed tumors quickly. Lastly, cytotoxic responsiveness towards primary cultures of mock and virus infected autologous and allogeneic cells implies that the cytotoxic effector is directed towards retrovirus infected cells.
Insights
Damselfish lymphocytes show anti-tumor activity against neurofibromatosis cell lines. This cytotoxic response is mediated by specific cells targeting retrovirus-infected cells, not by cells binding to tumors.
Area of Science:
- Comparative immunology
- Fish disease research
- Oncology
Background:
- Damselfish tumor cell lines are susceptible to lymphocyte-mediated cytotoxicity.
- A retrovirus associated with damselfish neurofibromatosis is present in tumor cell lines.
- The cellular effectors responsible for anti-tumor cytotoxicity require characterization.
Purpose of the Study:
- To identify and characterize the specific lymphocytes responsible for damselfish anti-tumor cytotoxicity.
- To investigate the role of retroviral infection in the cytotoxic response.
- To understand the immune mechanisms underlying damselfish neurofibromatosis.
Main Methods:
- Separation of lymphocytes using a specific antibody (5C6.10.4) targeting catfish non-specific cytotoxic cells.
- Assessment of cytotoxic activity against tumor cell lines and xenogeneic erythrocytes.
- Analysis of splenocyte cytotoxicity following inoculation with purified retrovirus.
- Evaluation of cytotoxicity against mock and virus-infected autologous and allogeneic cells.
Main Results:
- Damselfish 5C6.10.4 positive cells bind to tumor targets but do not induce cell death.
- The 5C6.10.4 negative lymphocyte population mediates the observed anti-tumor cytotoxicity.
- Prior exposure to the retrovirus enhances lymphocyte reactivity, particularly against infected cells.
- Long-term tumor-resisting animals exhibit significantly greater cytotoxic responses.
Conclusions:
- The primary cytotoxic effector against damselfish neurofibromatosis tumor cells is within the 5C6.10.4 negative lymphocyte population.
- The cytotoxic response is directed against retrovirus-infected cells, suggesting a role for viral antigens.
- Immune surveillance against retroviral infections may play a crucial role in controlling tumor development in damselfish.