Identification of a T-cell lymphoma in plkcGAPDH transgenic mice (Exome)

Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) is emerging as a key player in T-cell development, function and cancer. Here we investigated the role of GAPDH in T-cell development/function by overexpressing GAPDH in the T-cell lineage. Aged mice developed: 1) splenomegaly, 2) enlarged lymph nodes, 3) lymphocyte-infiltrations in the liver and bone marrow. All showed an increase of strongly proliferating and clonal Tfh CXCR5+PD1highCD4+-T cells associated with germinal center B cells and inflammatory cytokine-release. Gene-set-expression-analysis confirmed that this lymphoma was equivalent to human angioimmunoblastic T-cell lymphoma (AITL). Mechanistically, GAPDH induced NF-kB pathway in the murine AITL in vivo inhibition of NF-kB combined with anti-PD1 increased mice survival and cancer immune response. GAPDH-dependent modulation of NF-kB in T-cells allowed to model AITL-disease and evaluate treatments. Overall design: Whole exome sequencing of CD4+ T-cells isolated from plkcGAPDH transgenic mice