CD4+ T Cells and Antitumor Immunity - CD4+ T Cells, A More Central Role

CD4+ T Cells, A More Central Role

Today, there is adequate evidence to prove a more central role of the CD4+ T cell in antitumor immunity. In one important experiment, mice were given a tumor vaccine (irradiated tumor cells) several weeks prior to subcutaneous injection of tumour cells Immediately before exposure, some mice were treated with anti-CD4+ monoclonal antibodies, thus eliminating all CD4+ T cells. Mice in this group showed an extremely low rate of tumour rejection when compared those not treated with antibodies. (Dranoff et al. 1993) Despite the fact that CD4+ T cells were able to enhance the proliferation and differentiation of CD8+ cells, the immune response was extremely reduced. Furthermore, MHC class I deficient tumour cells have been shown to elicit immune responses in mice comparable to those elicited by tumours which have functional MHC class I (Hung, 1998). Subsequent depletion of CD4+ cells and NK cells, but not CD8+ cells results in the inability to reject the tumour.

In 1998, K. Hung demonstrated that vaccinated CD4-/- mice were unable to mount an effective immune response to a certain form of melanoma, while CD8-/- mice, could mount a response, weaker than the response of wild type mice, but nevertheless important. In this experiment, effectiveness was recognised by the number of mice surviving, following the second exposure to the cancer. The knockout of CD4+ T cells, on its own, does not prove a central role of these cells in antitumor immunity. It can be argued that, because CD4+ T cells were not present, CD8+ T cells could not mount as effective a response, and thus, the mice died. However, the fact that CD8-/- mice were still able to mount some form of response undisputedly shows a central role of CD4+ T cells in anti-tumour immunity. (Hung, 1998)