Monitoring the Functional Impact of TSHZ2 in naive CD4+ T cells across aging

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B608
Abstract ID: 5247

Presenting Author:
Nelson Mukuka , Post baccalaureate at Allen Inst. for Immunol.

Abstract:

As production of new T cells declines with age, long-term maintenance of T cells through controlled regulation of proliferation, activation and programmed cell death is critical. However, these processes are dysregulated in aging and age-related diseases such as cancer. Using TEA-seq (single cell analysis of protein, RNA and epigenome), we discovered that the human naïve CD4+ compartment, which is numerically maintained across age, displayed significant age-related changes in transcriptional and epigenetic programming. We found that multiple transcription factors, including a known tumor suppressor Teashirt zinc finger homeobox 2 (TSHZ2), exhibited substantially higher expression in older adults compared with children. These findings were further confirmed by Primeflow RNA analysis, showing increasing population of TSHZ2+ naive CD4 T cells across age. To investigate the function of TSHZ2 in T cells, Jurkat cell lines that mimicked young naïve CD4 T cells (TSHZ2neg) were transduced to overexpress TSHZ2. Preliminary results revealed significant alterations in cell proliferation, with transduced cells exhibiting a prolonged reduction in cell count compared to the wild-type control. These findings suggest that TSHZ2 regulates cell proliferation and division in T cells and may help maintain naive T cell longevity in the context of aging. Future studies into the functional role of TSHZ2 and its transcriptional targets in naive T cells are on-going.