Global gene expression analysis of peripheral blood cells, pluripotent cell lines, and iPS-derived T cells

Exhaustion of antigen-specific T cells represents a major challenge to adoptive immunotherapy against many types of cancer and viral infection. In an effort to overcome this problem, we reprogrammed clonally expanded antigen-specific CD8+ T cells from an HIV-1-infected patient to pluripotency. The T cell-derived induced pluripotent stem cells (T-iPSCs) were then redifferentiated into CD8+ T cells that had high proliferative capacity and elongated telomeres. To confirm that T-iPSCs were compatible to other embryonic stem cells (ESCs) but different from T cells, and that redifferentiated T cells were compatible to T cells but different from natural killer (NK) cells, we analyzed and compared the gene expression profiles of the samples by cDNA microarray. These analyses revealed that our T-iPSCs and redifferentiated T cells were essentially the same as their counterpart pluripotent stem cells and T cells, respectively. We generated human T-iPSC lines from peripheral blood T cells of healthy donors. To confirm that established T-iPSCs were typical iPSCs, the gene expression profile of one T-iPSC clone derived from a healthy person (TkT3V1-7) was compared to those of peripheral blood T cells (CD4+ T cell and CD8+ T cell) and ESCs (KhES3). We also established T-iPSCs (H254SeVT-3) from a T-cell clone (H25-#4) which was derived from an HIV-1-infected patient. H254SeVT-3 was redifferentitated into functional T cells (reT-1 and reT-2.1) in vitro. The gene expression profiles of reT-1 and reT-2.1 were compared to those of H25-#4 and peripheral blood NK cells to clarify that the redifferentiated T cells carried the same characteristics as the original T-cell clone.