Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes

Efficacy of IL‐2‐ versus IL‐15‐stimulated CD8 T cells in adoptive immunotherapy

“…2C). These data are well in line with previous reports that exposure of antigenstimulated P14 or pmel-1 T cells to IL-2 or IL-15 generates effector or central memory-like CD8 T cells, respectively [6,[8][9][10]12]. We also noted that P14 IL-2 and P14 IL-15 cells differed in functional CD95L/Fas ligand expression since co-culture of P14 IL-2 cells and L1210 target cells expressing CD95/Fas resulted in antigen-independent cell killing whereas co-culture of the same target cells and P14 IL-15 cells had no effect (Fig.…”

“…Phenotype and functional activity of P14 IL-2 and P14 IL-15 cells P14 IL-2 and P14 IL-15 cells were generated in vitro using the protocol originally described by Manjunath et al [6]. Briefly, CD8 T cells from P14 TCR-tg mice specific for the LCMV gp33 epitope were stimulated with gp33 peptide for 2 days to induce lymphoblasts.…”

“…Besides IL-2, IL-15 also supports CD8 T-cell growth [5]; however, the phenotype and the functional activity of IL-2-versus IL-15-cultured CD8 T cells differ considerably. Manjunath et al [6] were the first to show that CD8 T cells from P14 TCR-tg mice specific for gp33 epitope of lymphocytic choriomeningitis virus (LCMV) acquired an effector memory phenotype with high cytolytic activity when cultured in the presence of IL-2 whereas addition of IL-15 led to a central memory phenotype with low effector cell functions. Further analysis in the same TCR transgenic system revealed that these two cytokines were equivalent mitogens for antigen-stimulated CD8 T cells but that IL-2 was more potent in inducing amino acid uptake and protein synthesis [7].…”

Functional impairment of human T-lymphocytes following PHA-induced expansion and retroviral transduction: implications for gene therapy

“…Although the pattern of lineage differentiation of T cell functional subsets is still a matter of debate, evidence from others has confirmed the ability of CCR7 expression to discriminate populations with different functional properties. [23][24][25] In this study we have analyzed the effect of polyclonal expansion and subsequent transduction on the function of primary human T-lymphocytes, and then explored the underlying mechanisms. Our results show that PHA can lead to an impairment of the immune competence of these cells in vitro, as determined by allogeneic and viral antigen-specific responses.…”

“…Nevertheless, this does not imply that CD8 + T EM cells would not provide long-term immune responses, and we and others have shown that expression of CCR7 can be up-regulated by CD8 + T EM cells in some circumstances, a process that depends on the stimulus and the cytokine environment. [23][24][25]39 Further analysis of these rel-evant aspects is not possible from the design of our in vitro study.…”