Clonal expansion of antigen-specific CD8+ cytotoxic T lymphocytes is regulated by late exposure to serum to prevent apoptosis.
Although serum-free media have been used to expand lymphokine-activated killer cells, antigen-specific CD8 T cell cytotoxicity does not develop in vitro in the absence of serum. The immunodominant Vbeta17 response to an influenza A matrix protein epitope restricted by HLA A2.1 was used to study the serum requirement for CTL activation. Serum acts directly on T cells and not indirectly by activating APCs. In the absence of serum, the initial steps of T cell activation, including expression of CD69 and CD25, are unimpaired and some antigen-specific cytotoxicity may be generated in the first few days after stimulation. However, expression of late activation markers, such as HLA-DR and CD38, and clonal expansion of class I-restricted antigen-specific CTL does not occur if CTL are not exposed to serum within 4 days of antigen exposure. The antigen-specific CTL, but not unstimulated bystander T cells, undergo apoptosis if they are not exposed to serum within a few days of activation. Apoptosis of TCR-activated CTL does not appear to be Fas-mediated since it is not blocked by inhibiting the Fas pathway. Therefore, late exposure to an unidentified serum protein regulates the clonal expansion of TCR-activated CD8 CTL.
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The Center for Blood Research, Harvard Medical School, Boston, MA, USA.
Xu
Z
Z
Lieberman
J
J
D017209:Apoptosis / Q000276:immunology*; D001769:Blood; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D016895:Culture Media, Serum-Free; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009975:Orthomyxoviridae / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000276:immunology
D016895:Culture Media, Serum-Free; D018984:Epitopes, T-Lymphocyte; D007518:Isoantibodies; D014763:Viral Matrix Proteins