XENOSPECIFIC CD8+ CYTOTOXIC T LYMPHOCYTE GENERATION

Abstract

Background. Controversy exists as to whether natural killer(NK)1.1⁺cells additionally support cytotoxic T lymphocyte (CTL) generation. We have previously demonstrated that mice generate a strong in vitro xenospecific CTL response in local popliteal lymph nodes (LN) to footpad immunizations with large numbers of human tumor cells. Methods. In vivo depletion of various LN subsets using cytotoxic monoclonal antibodies was used to determine their relative importance in stimulating xenospecific CD8⁺CTL responses to human Jurkat tumor cells. Depletion of functional NK cells in vivo was evidenced by the relative lack of NK1.1⁺cells and NK activity in the spleens and LN of anti-NK1.1 monoclonal antibody-treated mice. Conclusion. Depletion of LN subsets indicated that CD4⁺T cells were critical in generating an effective xenospecific CD8⁺CTL response, but also suggested that NK1.1⁺cells play a significant additional accessory role in the development of mouse anti-human xenospecific CTL.