Impaired memory CD8 T cell development in the absence of methyl-CpG-binding domain protein 2.
Intracellular differentiation events that determine which cells develop into memory CD8 T cells are currently incompletely understood. Methyl-CpG-binding domain protein 2 (MBD2) is a transcriptional repressor that binds to methylated DNA and mediates the biological consequences of epigenetic gene methylation. The role of MBD2 during the differentiation of naive CD8 T cells into effector and memory cells was determined following acute infection of MBD2-deficient mice with lymphocytic choriomeningitis virus. Despite rapid viral clearance and an efficient primary effector CD8 T cell response, reduced numbers of Ag-specific memory CD8 T cells were observed. Importantly, the appearance of precursor memory cells (IL-7Ralphahigh) was delayed. The remaining MBD2(-/-) memory cells were not fully protective during rechallenge, and memory cell characteristics were altered with regard to surface markers (IL-7Ralpha, KLRG-1, CD27, and others) and cytokine production. The defect was CD8 T cell intrinsic, because memory cell development was also delayed when MBD2(-/-) CD8 T cells were adoptively transferred into SCID mice. These data demonstrate that MBD2 is a previously unrecognized intracellular factor required for the efficient generation of protective memory CD8 T cells.
Kersh
Ellen N
EN
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. ekersh@emory.edu
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D005260:Female; D007156:Immunologic Memory / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D013234:Stem Cells / Q000276:immunology / Q000473:pathology
D004268:DNA-Binding Proteins; C115368:MBD2 protein