Abstract
Immature thymocytes develop into mature T lymphocytes, including 2 major functional subpopulations: CD4+ helper and CD8+ cytotoxic T cells, prior to emigration from thymus. Previously we discovered a zinc finger transcription factor, ThPOK (T helper inducing POK factor, also known as zbtb7b, a member of the zbtb7 transcription factor subfamily), functioning as a master regulator in regulating CD4 vs CD8 T cell linage commitment process. However, the molecular mechanisms underlying this process still remain to be elucidated. Intriguingly, when mouse ThPOK was ectopically expressed as a transgene in T cell lineage, all Tg mice developed fatal T lymphomas. Here we reported that when the human zbtb7b sharing an 87% identity with the mouse counterpart at DNA level and a 97% homology at protein level, was expressed in mouse T cell lineage under the CD2 promoter, some Tg mice not only could correct the ThPOK deficient phenotype (MHC class II restricted T cells are CD8+), but also developed T lymphomas. Furthermore, when another zbtb7 transcription factor subfamily member, the mouse zbtb7a sharing an 83% homology with the mouse zbtb7b at protein level, was expressed in T cells, some Tg mice again corrected the ThPOK deficient phenotype and developed T lymphomas as well. Taken together, these results indicate the function of zbtb7b in regulating CD4 vs CD8 T linage commitment is evolutionarily reserved (supported by AI-33614).
