Migratory Properties of Naive, Effector, and Memory Cd8+ T Cells

Abstract

It has been proposed that two different antigen-experienced T cell subsets may be distinguishable by their preferential ability to home to lymphoid organs (central memory cells) or nonlymphoid tissues (effector memory/effector cells). We have shown recently that murine antigen-primed CD8+ T cells cultured in interleukin (IL)-15 (CD8IL-15) resemble central memory cells in phenotype and function. In contrast, primed CD8+ T cells cultured in IL-2 (CD8IL-2) become cytotoxic effector cells. Here, the migratory behavior of these two subsets was investigated. Naive, CD8IL-15 cells and, to a lesser degree, CD8IL-2 cells localized to T cell areas in the spleen, but only naive and CD8IL-15 cells homed to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of peripheral LNs revealed that CD8IL-15 cells, but not CD8IL-2 cells, rolled and arrested in high endothelial venules (HEVs). Migration of CD8IL-15 cells to LNs depended on L-selectin and required chemokines that bind CC chemokine receptor (CCR)7. Both antigen-experienced populations, but not naive T cells, responded to inflammatory chemokines and accumulated at sites of inflammation. However, CD8IL-2 cells were 12 times more efficient in migrating to inflamed peritoneum than CD8IL-15 cells. Furthermore, CD8IL-15 cells proliferated rapidly upon reencounter with antigen at sites of inflammation. Thus, central memory-like CD8IL-15 cells home avidly to lymphoid organs and moderately to sites of inflammation, where they mediate rapid recall responses, whereas CD8IL-2 effector T cells accumulate in inflamed tissues, but are excluded from most lymphoid organs.

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

“…These data are well in line with a previous report by Malek and co-workers in the OT-1 model [13]. These data may also help to reconcile the discrepancy between our data and a previous report by Weninger et al [12] in which P14 IL-2 cells could be recovered from the blood 24 h after transfer. In the latter study, activated P14 T cells were cultured for 6-8 days in IL-2 before transfer.…”

“…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.…”

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.…”

Down‐regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation

“…Chemokine receptor signaling induces functional effects such as migration, rolling, sticking, the invasion and proliferation of granulocytes, monocytes and lymphocytes as well as increasing the intracellular calcium concentration in these cells [16][17][18][19][20]. Chemokine receptors are also useful as surface markers to discriminate naive, memory and effector subsets in human CD8 + T cells.…”