Tumor-Specific CD4 super(+) T Cells Render the Tumor Environment Permissive for Infiltration by Low-Avidity CD8 super(+) T Cells

• Published in: The Journal of immunology (1950) Vol. 180; no. 5; pp. 3122 - 3131
• Main Authors: Wong, SBJustin, Bos, Rinke, Sherman, Linda A
• Format: Journal Article
• Language: English
• Published: 01.03.2008
• ISSN: 0022-1767

CD4 super(+) T cells enhance tumor destruction by CD8 super(+) T cells. One benefit that underlies CD4 super(+) T cell help is enhanced clonal expansion of newly activated CD8 super(+) cells. In addition, tumor-specific CD4 super(+) help is also associated with the accumulation of greater numbers of CD8 super(+) T cells within the tumor. Whether this too is attributable to the effects of help delivered to the CD8 super(+) cells during priming within secondary lymphoid tissues, or alternatively is due to the action of CD4 super(+) cells within the tumor environment has not been examined. In this study, we have evaluated separately the benefits of CD4 super(+) T cell help accrued during priming of tumor-specific CD8 super(+) T cells with a vaccine, as opposed to the benefits delivered by the presence of cognate CD4 super(+) cells within the tumor. The presence of CD4 super(+) T cell help during priming increased clonal expansion of tumor-specific CD8 super(+) T cells in secondary lymphoid tissue; however, CD8 super(+) T cells that have low avidity for tumor Ag were inefficient in tumor invasion. CD4 super(+) T cells that recognized tumor Ag were required to facilitate accumulation of CD8 super(+) T cells within the tumor and enhance tumor lysis during the acute phase of the response. These experiments highlight the ability of tumor-specific CD4 super(+) T cells to render the tumor microenvironment receptive for CD8 super(+) T cell immunotherapy, by facilitating the accumulation of all activated CD8 super(+) T cells, including low-avidity tumor-specific and noncognate cells.