Human CD8+ CD57- TEMRA cells: Too young to be called "old"

Abstract

End-stage differentiation of antigen-specific T-cells may precede loss of immune responses against e.g. viral infections after allogeneic stem cell transplantation (SCT). Antigen-specific CD8+ T-cells detected by HLA/peptide multimers largely comprise CD45RA-/CCR7- effector memory (TEM) and CD45RA+/CCR7- TEMRA subsets. A majority of terminally differentiated T-cells is considered to be part of the heterogeneous TEMRA subset. The senescence marker CD57 has been functionally described in memory T-cells mainly composed of central memory (TCM) and TEM cells. However, its role specifically in TEMRA cells remained undefined. Here, we investigated the relevance of CD57 to separate human CD8+ TEMRA cells into functionally distinct subsets. CD57- CD8+ TEMRA cells isolated from healthy donors had considerably longer telomeres and showed significantly more BrdU uptake and IFN-γ release upon stimulation compared to the CD57+ counterpart. Cytomegalovirus (CMV) specific T-cells isolated from patients after allogeneic SCT were purified into CD57+ and CD57- TEMRA subsets. CMV specific CD57- TEMRA cells had longer telomeres and a considerably higher CMV peptide sensitivity in BrdU uptake and IFN-γ release assays compared to CD57+ TEMRA cells. In contrast, CD57+ and CD57- TEMRA cells showed comparable peptide specific cytotoxicity. Finally, CD57- CD8+ TEMRA cells partially changed phenotypically into TEM cells and gained CD57 expression, while CD57+ CD8+ TEMRA cells hardly changed phenotypically and showed considerable cell death after in vitro stimulation. To the best of our knowledge, these data show for the first time that CD57 separates CD8+ TEMRA cells into a terminally differentiated CD57+ population and a so far functionally undescribed “young” CD57- TEMRA subset with high proliferative capacity and differentiation plasticity.

Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy

“…Coculture of HC CD8 + T cells with blasts did not significantly increase the percentage of cleaved caspase-3 + cells but more prominently induced their CD57 and 2B4 expression (P < 0.001 and P = 0.01, respectively) ( Figure 3C). These findings are in line with previous observations of increased CD57 expression on T cells in the hematologic malignancies milieu (44,45) and increased susceptibility to apoptosis of CD8 + CD57 + cells upon activation or antigen stimulation (46,47).…”

Peculiarities of the phenotype of T-lymphocytes in the dynamics of the postoperating period in patients with peritonite depending on the outcome of disease

“…К концу периода наблюдения у больных РГП в крови повышается содержание Т-лимфоцитов, экспрессирующих рецептор CD57. CD57 (также известный как HNK1 (human natural killer-1), L2, LEU7) представляет собой углеводный эпитоп, характеризующий накопление перфоринов и гранзимов, и экспрессируется на терминальной стадии дифференцировки клеток [11,29]. У больных с благоприятным исходом заболевания повышение количества CD57 + Т-лимфоцитов проявляется на 2 неделе после- операционного лечения, тогда как при неблагоприятном исходе РГП -на 3 неделе.…”

Do opportunistic viruses hunt in packs?

“…One of these is an abundance of TEMRA cells, defined as CD8+, CCR7‐ effector memory T‐cells that re‐express the CD45RA isoform. TEMRA cells that also expressed CD57 were terminally differentiated and had shorter telomeres, whereas those that did not express CD57 were able to proliferate and to differentiate . The authors suggest that CD57 expression on TEMRA CD8+ lymphocytes is a functional marker of immunosenescence.…”