期刊
JOURNAL OF IMMUNOLOGY
卷 164, 期 1, 页码 208-216出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.164.1.208
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资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI027028, R56AI027028, R21AI027028] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [T32MH019185] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI-27028, R01 AI027028] Funding Source: Medline
- NIMH NIH HHS [T32 MH019185, T32MH-19185-09] Funding Source: Medline
Dissecting the mechanisms of T cell-mediated immunity requires the identification of functional characteristics and surface markers that distinguish between activated and memory T lymphocytes. In this study, we compared the rates of cytokine production by virus-specific primary and memory CD8(+) T cells directly ex vivo. Ag-specific IFN-gamma and TNF-alpha production by both primary and long-term memory T cells was observed in less than or equal to 60 min after peptide stimulation. Although the on-rate kinetics of cytokine production were nearly identical, activated T cells produced more IFN-gamma, but less TNF-alpha, than memory T cells. Ag-specific cytokine synthesis was not a constitutive process and terminated immediately following disruption of contact with peptide-coated cells, demonstrating that continuous antigenic stimulation was required by both T cell populations to maintain steady-state cytokine production. Upon re-exposure to Ag, activated T cells resumed cytokine production whereas only a subpopulation of memory T cells reinitiated cytokine synthesis. Analysis of cytokine profiles and levels of CD8, LFA-1, and CTLA-4 together revealed a pattern of expression that clearly distinguished in vivo-activated T cells from memory T cells. Surprisingly, CTLA-4 expression was highest at the early stages of the immune response but fell to background levels soon after viral clearance. This study is the first to show that memory T cells have the same Ag-specific on/off regulation of cytokine production as activated T cells and demonstrates that memory T cells can be clearly discriminated from activated T cells directly ex vivo by their cytokine profiles and the differential expression of three well-characterized T cell markers.
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