Submitted October 3, 2002
Accepted January 14, 2003
Tumour and CD4 T-cell interactions: tumour escape as result of reciprocal inactivation
Sarah Flynn and Brigitta Stockinger*
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom
* Corresponding author; email: bstocki{at}nimr.mrc.ac.uk.
This paper addresses the capacity of naive, effector and memory CD4 T cells to control growth of a MHC class II positive B cell lymphoma in vivo. To assess the role of T cells on their own without contributions by B cells, antibodies or NK cells we generated pure effector or memory CD4 T cells in Rag-/- gc-/- mice deficient in endogenous lymphocytes and NK cells. Lymphoma cells expressing a model antigen were injected into mice with T cells of cognate specificity that were either naive or in effector or resting memory state. Naive T cells were unable to prevent tumour growth, probably due to delay of efficient cross-presentation by dendritic cells. However, both effector and memory T cells, dependent on the amount of antigen available, controlled the tumour for a considerable period of time without the need for dendritic cell stimulation. Nevertheless, tumour eventually grew uncontrolled in all cases. This was not because of a defect in T cell homing to the tumour site or loss of MHC class II or costimulatory molecules by the tumour, but reflected mutual paralysis of T cell responsiveness and antigen processing by tumour cells.
