Tumor-specific CD4+ T cells render the tumor environment permissive for infiltration by low-avidity CD8+ T cells.
CD4+ T cells enhance tumor destruction by CD8+ T cells. One benefit that underlies CD4+ T cell help is enhanced clonal expansion of newly activated CD8+ cells. In addition, tumor-specific CD4+ help is also associated with the accumulation of greater numbers of CD8+ T cells within the tumor. Whether this too is attributable to the effects of help delivered to the CD8+ cells during priming within secondary lymphoid tissues, or alternatively is due to the action of CD4+ cells within the tumor environment has not been examined. In this study, we have evaluated separately the benefits of CD4+ T cell help accrued during priming of tumor-specific CD8+ T cells with a vaccine, as opposed to the benefits delivered by the presence of cognate CD4+ cells within the tumor. The presence of CD4+ T cell help during priming increased clonal expansion of tumor-specific CD8+ T cells in secondary lymphoid tissue; however, CD8+ T cells that have low avidity for tumor Ag were inefficient in tumor invasion. CD4+ T cells that recognized tumor Ag were required to facilitate accumulation of CD8+ 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+ T cells to render the tumor microenvironment receptive for CD8+ T cell immunotherapy, by facilitating the accumulation of all activated CD8+ T cells, including low-avidity tumor-specific and noncognate cells.
Wong
S B Justin
SB
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Bos
Rinke
R
Sherman
Linda A
LA
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D007340:Insulinoma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051381:Rats
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte