CCL2 inhibits the apoptosis program induced by growth factor deprivation, rescuing functional T cells.
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.
Diaz-Guerra
Eva
E
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Vernal
Rolando
R
del Prete
M Julieta
MJ
Silva
Augusto
A
Garcia-Sanz
Jose A
JA
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D007376:Interleukin-2 / Q000276:immunology*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D054390:Receptors, CCR2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000276:immunology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2; D008024:Ligands; D012333:RNA, Messenger; D054390:Receptors, CCR2