Subsets of CD8+, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses

Abstract

SUMMARYTwo different subsets of CD8+, CD57+ cells have been defined, one expressing high levels (CD8W0+(CD57+)), the other expressing low levels of surface CD8 (CD81o0+(CD57+)). Increased numbers of CD8,gh+(CD57+) cells correlated with previous HCMV infection. By three-colour fluorescence analysis, the CD8high+(CD57+) population expressed T cell markers such as CD3 and CD5, and most were axf T cell receptor (afi TCR)-positive. A significant proportion also expressed CD71 (transferrin receptor) and MHC class II, although little if any CD25 (IL-2R-p55). Some ( > 40%) co-expressed CD45RA and CD45RO. The CD810,+(CD57+) population expressed classical natural killer (NK) cell markers-CD2, CD16 and CD56. The two subsets were also functionally distinct; CD8,gh+(CD57+) cells suppressed pokeweed mitogen (PWM)-driven, but not phytohaemagglutinin (PHA)-driven proliferation and immunoglobulin production; CD81,w+(CD57+) cells exhibited NK cytotoxic activity which was not increased by interferon-alpha (IFN-a). Supernatant from cultured CD8igh+(CD57+) cells suppressed PWM-driven immunoglobulin production, but not proliferation, and this effect was abrogated by physical separation with tissue culture inserts. Thus, a T cell subset expressing activation and memory T cell markers with direct non-specific suppressor activity was present in peripheral blood mononuclear cells (PBMC) of healthy subjects with asymptomatic HCMV infection.

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

“…CMV-infected individuals have enriched populations of CD57 + T cells and NKG2C + CD57 + NK cells (21)(22)(23)(24). In accordance with these studies we found expanded subsets of CD8 + CD57 + T cells and NKG2C + and NKG2C + CD57 + NK cells prior to EBV infection among PBMC of our CMV + 2-y-old children (Fig.…”

“…The CMV-driven differentiation of T and NK cells involves acquisition of distinct functional profiles. In the case of cytotoxic T cells this includes lower activation threshold and higher degranulation and cytokine production capacity as well as bystander responses, whereas this is not always the case for NK cells (22,25,26). Therefore, an expansion of specific subsets of effector cells in CMV + individuals could affect the quality of subsequent responses toward other infectious agents as previously suggested (27,28).…”

“…CMV-infected individuals have large populations of CD8 + CD57 + T cells (21,22). These cells are potent effectors owing to high expression of cytolytic molecules and IFN-g (25, 44).…”

“…Interestingly, CMV can act as a driving force for differentiation of T and NK cells. Acutely and latently CMV-infected individuals have enriched populations of late-differentiated T cells expressing the CD57 Ag and NK cells expressing the activation receptor NKG2C, either alone or together with CD57 (21)(22)(23)(24). The CMV-driven differentiation of T and NK cells involves acquisition of distinct functional profiles.…”

Refining the diagnosis of T-cell large granular lymphocytic leukemia by combining distinct patterns of antigen expression with T-cell clonality studies

“…Some studies have defined CD8 þ T cells with expression of CD57 as replicatively scenescent T cells, 19 whereas others demonstrate these cells to be effector cytotoxic T cells that are increased in infections or neoplasms and represent a chronically activated state. [20][21][22][23][24] Still, others have shown that expansions of CD8 þ /CD57 þ T cells are seen with increased frequency in the elderly, and they have postulated defects in immune system homeostasis leading to expansion of these T cells and diminished immune system surveillance. 25 Nonetheless, we are not aware of significant studies on T cells with the phenotype of CD8 þ (dim)/CD57 þ expression.…”