Neonatal thymectomy, which inhibits maturation of select aspects of the immune response, renders animals more susceptible to the carcinogenic action of oncogenic viruses and select chemical carcinogens. In man, several thymus-related immunologic deficiency diseases have been shown to be characterized by a markedly increased frequency of malignant tumors, as has been chronic immunosuppressive therapy. On the basis of the above and related observations, the recirculating thymic-dependent small lymphocyte (T cell) has been implicated in the pathogenesis of a variety of spontaneous and artifically induced tumors and it has been postulated that this cell type constitutes an integral part of the immune surveillance mechanism. The remarkable radiosensitivity of the small lymphocyte has been well documented, as has been the carcinogenic effect of ionizing radiation. The mechanisms involved in such tumorigenesis are not clear, however, and in particular the relationship between the immunosuppressive effects of exposure to biologically significant amounts of whole body radiation and the neoplastic consequences of such exposure remain poorly defined. The purpose of the proposal is threefold: 1) to investigate the effect of neonatal and adult thymectomy on the prevalence of spontaneous and radiation-related tumors in germfree and conventional mice; 2) to determine if the tumorigenic effects of radiation can be modified via reconstitution with defined populations of lymphocytes post-exposure; suppressor and helper T cells are of particular interest in this regard; 3) to correlate the above with the immune status of the host, particularly with respect to the number of recirculating T cells mobilizable via thoracic duct cannulation. Other methods of evaluation include: temporal evaluation of the immunologic capabilities of thymic-dependent lymphocytes from each experimental group including evaluation of relative numbers of suppressor and helper cells; morphologic evaluation of all deaths to include histologic evaluation of tumors; age-specific death rate for neoplasms.
NIH ExPorter
NIH ExPorter