CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells

Abstract

The precise mechanisms involved in the switch between the clonal expansion and contraction phases of a CD8+ T cell response remain to be fully elucidated. One of the mechanisms implicated in the contraction phase is cytokine deprivation, which triggers apoptosis in these cells. CCR2 chemokine receptor is up-regulated following IL-2 deprivation, and its ligand CCL2 plays an essential role preventing apoptosis induced by IL-2 withdrawal not only in CTLL2 cells, but also in mouse Ag-activated primary CD8+ T cells because it rescued functional CD8+ T cells from deprivation induced apoptosis, promoting proliferation in response to subsequent addition of IL-2 or to secondary antigenic challenges. Thus, up-regulation of the CCR2 upon growth factor withdrawal together with the protective effects of CCL2, represent a double-edged survival strategy, protecting cells from apoptosis and enabling them to migrate toward sites where Ag and/or growth factors are available.

BMP15 Prevents Cumulus Cell Apoptosis Through CCL2 and FBN1 in Porcine Ovaries

“…CCL2 protection from tat-induced apoptosis in neurons correlates with a reduction in uptake and changes in the intracellular distribution of tat [25]. CCL2 also inhibits the T cell apoptotic program induced by growth factor deprivation [26] and blocks the constitutive apoptosis of normal neutrophils through CCR2 [27]. These results agree with our data and substantiated our results.…”

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).…”

Increased Antitumor Effects Using IL-2 with Anti–TGF-β Reveals Competition between Mouse NK and CD8 T Cells

“…It is possible that IL2 dependent IFNγ production can lead to immune cell loss following treatment cessation. Furthermore, cytokine deprivation is also important for antigen-stimulated T cell contraction (40). Due to the loss of effect after immunotherapy, it is clear that approaches similar to the one developed by Park et al might be necessary to achieve prolonged anti-tumor effects (20).…”