The Role for Monocyte Chemoattractant Protein-1 in the Generation and Function of Memory CD8+ T Cells

Abstract

Memory T cells are resistant to the conventional costimulatory blockade and therefore impede tolerance induction. However, their migratory, survival, and functional requirements for chemokines are not well understood. We herein examine the role for MCP-1 or CCL2 in the generation, migration, and function of memory CD8+ T cells. We found that overall generation of both central memory (TCM) and effector memory (TEM) CD8+ T cells was severely impaired in the absence of MCP-1. Importantly, the survival of TEM, but not TCM, CD8+ cells was reduced without MCP-1, whereas the homeostatic proliferation of TCM, but not TEM, CD8+ cells was weakened in MCP-1−/− mice. However, once they were generated in the absence of MCP-1, in vitro function of both subsets of memory cells remained intact as determined by their proliferation and IFN-γ production. Interestingly, the migration of TCM, but not TEM, CD8+ cells to inflammatory sites was significantly delayed without MCP-1, whereas both subsets of memory cells underwent comparable expansion and apoptosis with or without MCP-1 during the effector phase. Moreover, the function to eliminate a graft of TCM, but not TEM, CD8+ cells was impaired without MCP-1. Thus, this study demonstrates that MCP-1 plays an important role in not only migration but also generation and survival of memory T cells. This finding provides new insight into the requirement of chemokines for the generation, survival, and function of differential subsets of memory T cells and may have clinic implications for tolerance induction.

CCR2 Identifies a Stable Population of Human Effector Memory CD4+ T Cells Equipped for Rapid Recall Response

“…The relative resistance of the CCR5 + CCR2 + cells to death was associated with high levels of BCL-2 and cFLIP, antiapoptotic proteins within the intrinsic (cytokine withdrawal) and extrinsic (Fas-or TCR-mediated) pathways, respectively. It is of interest that CCL2/MCP-1 has been reported to protect activated mouse CD8 + T cells from death due to cytokine withdrawal (76) and to be important for survival of CD8 + T EM in mice (77). However, in our assays of spontaneous and FASmediated death, we saw no protective effect of adding CCL2/MCP-1 (data not shown).…”

Expansion of decidual CD45RO+ T cells with high expression of CEACAM1 in the early stage of pregnancy

“…These data suggested that trophoblasts and monocytes were likely to be involved in the generation of CD45RO + T cells. The secretion of MCP-1 was determined by ELISA, as it has been demonstrated to be significant in the generation of CD45RO + T cells (16). Consistent with a previous study (15), we observed that the production of MCP-1 in the MHM was notably higher than that in the monocyte or human trophoblast HTR8/SVneo cell line cultures (Fig.…”

“…It has been demonstrated that the interaction of trophoblast cells and monocytes markedly enhances the expression of cytokines/chemokines, including MCP-1 (15). MCP-1, the main monocyte chemoattractant, has been demonstrated to be associated with the generation and survival of CD45RO + T cells (16). In the present study, to investigate the possible expansion and activation mechanisms of decidual CD45RO + T cells, we developed an effective in vitro model to generate these cells.…”

“…Although the effects of trophoblast cells on the recruitment of immune cells have been extensively investigated (8,12,13), the effect of trophoblast cells on the expansion and differentiation of decidual leukocytes remains unknown (14). A previous study demonstrated that the interactions between trophoblast cells and monocytes significantly increased the secretion and production of cytokines and chemokines (15), including monocyte chemoattractant protein-1 (MCP-1), which is important in the generation and survival of CD45RO + T cells (16). Whether the crosstalk between trophoblast cells and monocytes participates in the expansion of decidual CD45RO + T cells remains to be elucidated.…”

Monocyte Chemoattractant Protein–1 Blockade Inhibits Lung Cancer Tumor Growth by Altering Macrophage Phenotype and Activating CD8+ Cells

“…The role of chemokines such as CCL5, CXCL8, and CXCL10 in the pathogenesis of lung cancer, and in other cancers, has been increasingly appreciated (27,28). However, the role of other important chemokines in lung cancer, such as CCL2, remains unclear.…”