In vitro generated human memory-like T cells are CD95 type II cells and resistant towards CD95-mediated apoptosis.
An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These long-term cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl-x(L) and Bcl-2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.
Fas
Stefanie C
SC
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany. stefanie.fas@gmail.com
Baumann
Sven
S
Krueger
Andreas
A
Frey
Christian R
CR
Schulze-Bergkamen
Henning
H
Brenner
Dirk
D
Stumpf
Christine
C
Kappes
Kathrin
K
Krammer
Peter H
PH
D017209:Apoptosis; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000494:pharmacology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D051020:bcl-X Protein / Q000032:analysis / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor