T-cell receptor diversity prevents T-cell lymphoma development
Newrzela S et al. – This study introduces a new innate mechanism of lymphoma control.Methods
- In a previous study we found that mature T cells are resistant to transformation with known T-cell oncogenes.
- We observed that T-cell receptor (TCR) mono-/oligoclonal mature T cells from TCR transgenic (tg) mice (OT-I, P14) expressing the oncogenes NPM/ALK or deltaTrkA readily developed MTCLs in T-cell-deficient recipients.
- Analysis of cell surface markers largely ruled out that TCR tg lymphomas were derived from T-cell precursors.
- Furthermore, cotransplanted non-modified TCR polyclonal T cells suppressed malignant outgrowth of oncogene expressing TCR tg T lymphocytes.
- A dominant role of an anti-leukemic immune response or Tregs in the control of MTCLs seems unlikely as naïve T cells derived from oncogene expressing stem cells, which should be tolerant to leukemic antigens, as well as purified CD4 and CD8 were resistant to transformation.
- However, our results are in line with a model in which homeostatic mechanisms that stabilize the diversity of the normal T-cell repertoire, for example, clonal competition, also control the outgrowth of potentially malignant T-cell clones.