EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function

AD Hislop, NH Gudgeon, MFC Callan… - The Journal of …, 2001 - journals.aai.org
AD Hislop, NH Gudgeon, MFC Callan, C Fazou, H Hasegawa, M Salmon, AB Rickinson
The Journal of Immunology, 2001journals.aai.org
EBV infection in humans induces CD8+ T cell memory to viral epitopes derived from both
lytic and latent cycle Ags. We have analyzed the relationship between the phenotype and
function of the memory pool of T cells specific for these Ags. Lytic epitope-specific
populations were heterogeneous in terms of CD45RO/RA and CD28 expression, whereas
latent epitope-specific populations were uniformly CD45RO+ and CD28+, consistent with
the higher antigenic challenge from lytic epitopes driving some memory cells toward a …
Abstract
EBV infection in humans induces CD8+ T cell memory to viral epitopes derived from both lytic and latent cycle Ags. We have analyzed the relationship between the phenotype and function of the memory pool of T cells specific for these Ags. Lytic epitope-specific populations were heterogeneous in terms of CD45RO/RA and CD28 expression, whereas latent epitope-specific populations were uniformly CD45RO+ and CD28+, consistent with the higher antigenic challenge from lytic epitopes driving some memory cells toward a CD45RA+, CD28− phenotype. However, both types of memory population showed immediate epitope-specific cytotoxicity and type 1 cytokine production in ex vivo assays. Cytotoxic function was not associated with preactivated T cells, as EBV-specific populations were negative for activation markers such as CD69 or CD38, nor could cytotoxic function be ascribed to CD27− or CD56+ subsets, as such cells were not detected in EBV-specific memory. Furthermore, cytotoxicity was not limited to CD45RA+ and/or CD28− fractions, but also was observed in CD45RO+, CD28+ populations in lytic and latent epitope-specific memory. Cytokine (IFN-γ, TNF-α) responses, measured by intracytoplasmic staining after peptide stimulation, also were detectable in CD45RO+ and RA+ subsets as well as CD28+ and CD28− subsets. Of other markers that were heterogeneous in both lytic and latent epitope populations, CCR7 gave the best discrimination of functionality; thus, CCR7+ cells consistently failed to give an IFN-γ or TNF-α response, whereas many CCR7− cells were responsive. Our data are consistent with effector functions having a broad distribution among phenotypically distinct subsets of “effector memory” cells that have lost the CCR7 marker.
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