TY - JOUR
T1 - Activated and memory CD8+ T cells can be distinguished by their cytokine profiles and phenotypic markers
AU - Slifka, Mark K.
AU - Whitton, J. Lindsay
PY - 2000/1/1
Y1 - 2000/1/1
N2 - 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-γ and TNF-α production by both primary and long-term memory T cells was observed in ≤60 min after peptide stimulation. Although the on-rate kinetics of cytokine production were nearly identical, activated T cells produced more IFN-γ, but less TNF-α, 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.
AB - 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-γ and TNF-α production by both primary and long-term memory T cells was observed in ≤60 min after peptide stimulation. Although the on-rate kinetics of cytokine production were nearly identical, activated T cells produced more IFN-γ, but less TNF-α, 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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U2 - 10.4049/jimmunol.164.1.208
DO - 10.4049/jimmunol.164.1.208
M3 - Article
C2 - 10605013
AN - SCOPUS:0033961476
SN - 0022-1767
VL - 164
SP - 208
EP - 216
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -