iNKT Cell Lineage Research Articles

PLZF is essential for iNKT cell development (82.5)

Abstract The promyelocytic leukaemia zinc finger (PLZF) protein is a member of the BTB/POZ zinc finger family of transcription factors. This family of transcription factors also include Th-Pok, BCL-6 and MAZR which are known to play important roles in the immune system. Here we demonstrate that PLZF deficient mice have a severe impairment in iNKT cell lineage development leading to a lack of iNKT cells in the thymus and periphery. Real-time PCR showed that PLZF mRNA is highly expressed in iNKT cells. This correlates with flow cytometry analysis which revealed exclusive expression of PLZF protein in iNKT cells within the immune system. Radiation chimeras showed that PLZF is required for iNKT cell development in a cell intrinsic manner. These results identify PLZF as a key factor in iNKT development. They also underline the BTB/POZ family of transcription factors as important factors in the immune system.

Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny.

T lineage commitment occurs in a discrete, stage-specific manner during thymic ontogeny. Intrathymic precursor transfer experiments and the identification of CD4(+)8+ double-positive (DP), V alpha 14J alpha 18 natural T (iNKT) cells suggest that commitment to this lineage might occur at the DP stage. Nevertheless, this matter remains contentious because others failed to detect V alpha 14J alpha 18-positive iNKT cells that are CD4(+)8+. In resolution to this issue, we demonstrate that retinoic acid receptor-related orphan receptor gamma (ROR gamma)0/0 thymi, which accumulate immature single-positive (ISP) thymocytes that precede the DP stage, do not rearrange V alpha 14-to-J alpha 18 gene segments, suggesting that this event occurs at a post-ISP stage. Mixed radiation bone marrow chimeras revealed that RORgamma functions in an iNKT cell lineage-specific manner. Further, introgression of a Bcl-x(L) transgene into ROR gamma(0/0) mice, which promotes survival and permits secondary rearrangements of distal V alpha and J alpha gene segments at the DP stage, rescues V alpha 14-to-J alpha 18 recombination. Similarly, introgression of a rearranged V alpha 14J alpha 18 transgene into ROR gamma(0/0) mice results in functional iNKT cells. Thus, our data support the "T cell receptor-instructive (mainstream precursor) model" of iNKT cell lineage specification where V alpha 14-to-J alpha 18 rearrangement, positive selection, and iNKT cell lineage commitment occur at or after the DP stage of ontogeny.

Rapidly expanding exophthalmos: an unusual presentation of small cell lung cancer.

A 61-year-old male presented with a rapidly progressive exophthalmos from small cell lung cancer metastatic to the right orbit. His vision in that eye was 20/200, and his intraocular pressure was 36 mmHg. The orbital metastasis responded dramatically to chemotherapy. One week after starting the chemotherapy the patient did not have exophthalmos, his vision was 20/20, and three weeks later the intraocular pressure was 12 mmHg.