TY - JOUR
T1 - Human late memory CD8+ T cells have a distinct cytokine signature characterized by CC chemokine production without IL-2 production
AU - Kim, Tae Kon
AU - St. John, Lisa S.
AU - Wieder, Eric D.
AU - Khalili, Jahan
AU - Qing, Ma
AU - Komanduri, Krishna V.
PY - 2009/11/15
Y1 - 2009/11/15
N2 - Late memory T cell skewing is observed in the setting of immune recovery after cord blood transplantation, and may be associated with inferior control of viral reactivation and cancers. Therefore, we sought to understand how late memory cells differ functionally from earlier stage memory T cells, and whether surface phenotypes associated with differentiation stages were predictably associated with functional signatures. Higher order cytokine flow cytometry allows characterization of human T cells based on complex phenotypic markers and their differential capacity to simultaneously secrete effector proteins, including cytokines and chemokines. We used 8-color, 10-parameter cytokine flow cytometry to characterize the functional activation of human late memory CD8+ T cells defined by CD45RA and CD27 expression (CD27 -CD45RA+). We assessed the 15 possible functional signatures of cells defined by production of IL-2, IFN-γ, TNF-α, and MIP-1β alone or in combination, following activation with Ags stimulating bypassing surface proteins (PMA:ionomycin) or through the TCR (e.g., viral Ags). Late memory CD8+ T cells produced abundant amounts of CC chemokines (MIP-1β, MIP-1α, and RANTES) but not IL-2. IL-2/IFN-γ coproduction, characteristic of protective immune responses to viral infections, was absent in late memory CD8+ T cells. These data demonstrate that functional cytokine signatures are predictably associated with CD8+ maturation stages, and that the polarization of late memory CD8+ T cells toward CC chemokine production and away from IL-2 production suggests a unique functional role for this subset.
AB - Late memory T cell skewing is observed in the setting of immune recovery after cord blood transplantation, and may be associated with inferior control of viral reactivation and cancers. Therefore, we sought to understand how late memory cells differ functionally from earlier stage memory T cells, and whether surface phenotypes associated with differentiation stages were predictably associated with functional signatures. Higher order cytokine flow cytometry allows characterization of human T cells based on complex phenotypic markers and their differential capacity to simultaneously secrete effector proteins, including cytokines and chemokines. We used 8-color, 10-parameter cytokine flow cytometry to characterize the functional activation of human late memory CD8+ T cells defined by CD45RA and CD27 expression (CD27 -CD45RA+). We assessed the 15 possible functional signatures of cells defined by production of IL-2, IFN-γ, TNF-α, and MIP-1β alone or in combination, following activation with Ags stimulating bypassing surface proteins (PMA:ionomycin) or through the TCR (e.g., viral Ags). Late memory CD8+ T cells produced abundant amounts of CC chemokines (MIP-1β, MIP-1α, and RANTES) but not IL-2. IL-2/IFN-γ coproduction, characteristic of protective immune responses to viral infections, was absent in late memory CD8+ T cells. These data demonstrate that functional cytokine signatures are predictably associated with CD8+ maturation stages, and that the polarization of late memory CD8+ T cells toward CC chemokine production and away from IL-2 production suggests a unique functional role for this subset.
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U2 - 10.4049/jimmunol.0902068
DO - 10.4049/jimmunol.0902068
M3 - Article
C2 - 19841187
AN - SCOPUS:71249111250
SN - 0022-1767
VL - 183
SP - 6167
EP - 6174
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -