Inhibition of alpha nascent polypeptide associated complex protein may induce proliferation, differentiation and enhance the cytotoxic activity of human CD8+ T cells

Al-Shanti, Nasser and Aldahoodi, Ziyad (2006) Inhibition of alpha nascent polypeptide associated complex protein may induce proliferation, differentiation and enhance the cytotoxic activity of human CD8+ T cells. Journal of clinical immunology, 26 (5). pp. 457-464. ISSN 1573-2592

File not available for download.

Abstract

The molecular mechanisms that control CD8+ T cell proliferation and differentiations are poorly understood. Consequently, better understanding of the molecular pathways that regulate these processes may have an impact on the numbers and efficiency of antigen-specific cells that can be generated for cellular immunotherapy applications. Using differential display, we previously determined that alpha nascent polypeptide associated complex (α NAC) was identified as a potential target as its protein expression was found to be down-regulated as differentiation progressed in cultured human CD8+ T cells. Here anti-sense technology was used to further investigate the role which α NAC may play in proliferation and differentiation. Human purified CD8+ T cells were cultured in the presence of sense, non-sense and anti-sense oligonucleotides against the mRNA of α NAC. We reported that in the presence of anti-sense oligonucleotides expanded CD8+ T cells exhibited higher levels of differentiation and activation markers and also increased proliferation response compared to cells cultured with sense-oligonucleotides. Furthermore, the functional cytotoxicity of CD8+ T cells cultured with anti-sense was increased to 66% (±4.7%) compared to 42% (±3.2%) in cells expanded in the presence of oligonucleotides controls. Taken together, our results demonstrated that inhibition of α NAC protein induced not only cell proliferation but also differentiation and cytotoxic activity of CD8+ T cells.