Anti-Human Papillomavirus T Cell Effector Responses

Mosmann, Tim

Abstract

Different strains of Human Papillomavirus (HPV) cause skin warts, anogenital warts and cervical dysplasia, and are the main cause of cervical cancer. Several lines of evidence indicate that the immune system can limit the spread of the infected lesions, and in some cases can destroy warts. During the immune response against pathogens, the immune response has a wide variety of potential mechanisms to attack and kill the pathogen. For each pathogen, certain responses are effective, whereas others are ineffective because of defense strategies by the pathogen. Therefore the immune response must choose the correct mechanism for a particular injection so that the pathogen can be eradicated with minimal damage to the host. The choice between different types of immune response is regulated in a large part by T lymphocytes secreting different sets of cytokines. In this project we will define the T cell effector responses that are associated with the regression of established warts, and with protective immunity against HPV infection. The type of immune response that is mounted against HPV will be analyzed using a new assay for detecting simultaneous secretion of multiple cytokines by individual cells circulating in the blood. The potential of HPV-specific T cells to differentiate into additional effector types will be measured, to test the hypothesis that immune responses include many uncommitted T cells that can subsequently differentiate into divergent phenotypes. These studies will then be extended to the lymphocytes that infiltrate warts and cause regression, with the expectation that these T cells will include the cells mediating destruction of the lesion. Together, this information should identify the particular immune effector functions that are associated with an effective response against HPV, and also define the potential for modification of immune responses by therapeutic vaccines.