Functional analysis of the CD8⁺CD57⁺ cell population in normal healthy individuals and matched unrelated T‐cell‐depleted bone marrow transplant recipients

Abstract

Summary. The biological activities of CD81 that co-express CD57 remain poorly defined. It is unclear whether all CD8 1 cells have the potential to become CD57 1 or whether they represent a unique subset with distinct functions. Several studies have reported the association between elevated numbers of CD81 CD57 1 and a wide range of clinical disorders such as viral reactivation of human cytomegalovirus (HCMV). In this study, we have investigated the relationship between viral reactivation and the effect of diminished interleukin (IL)-2 production. Using CD8 1 cells isolated from patients at various times after allogeneic transplants and in vitro models of HCMV infection, we determined their combined effect on CD8 1 CD57 1 . Our results show that high numbers of CD8 1 CD57 1 correlated with diminished killing of HCMV-infected targets. In addition, we showed a synergistic effect between IL-2 and HCMV in the expansion of CD81 CD57 1 cells. Furthermore, these cells after anti-CD3 stimulation did not produce tumour necrosis factor (TNF)-a or interferon (IFN)-g. Interestingly, IL-10 production was elevated in several patients which appeared to be associated with the time from transplant.

Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation

“…We found rapid normalization or even overexpression of activated CD8 þ cells expressing CD57 or HLA-DR in the first months post transplantation. Early CD8 þ T-cell restoration led to a reversed CD4/CD8 ratio after RIC-PBSCT and may result from an initial expansion of transferred or residual CD8 þ T cells, as described by Rowbottom et al 35 Biological activity of CD8 þ /CD57 þ cells is unclear, but is supposed to contain anti-CMV cytotoxic T cells. 35,36 CD8 High /CD57 þ T cells arise from peripheral expansion and contribute to the oligoclonal antigen-dependent repertoire, while CD8 Low /CD57 þ are corresponding to NK cells, a cell subset also rapidly reconstituted in our study as usually observed after HSCT.…”

“…Early CD8 þ T-cell restoration led to a reversed CD4/CD8 ratio after RIC-PBSCT and may result from an initial expansion of transferred or residual CD8 þ T cells, as described by Rowbottom et al 35 Biological activity of CD8 þ /CD57 þ cells is unclear, but is supposed to contain anti-CMV cytotoxic T cells. 35,36 CD8 High /CD57 þ T cells arise from peripheral expansion and contribute to the oligoclonal antigen-dependent repertoire, while CD8 Low /CD57 þ are corresponding to NK cells, a cell subset also rapidly reconstituted in our study as usually observed after HSCT. 27 In agreement with previous studies, 20,37,38 we observed rapid NK cell reconstitution, since the median CD3À CD56 þ cell counts were close to the normal values as soon as M þ 1.5.…”

Optimization of Functional Efficacy of Phosphorothioate‐Modified Oligonucleotides in a Human CD8+ T‐Cell Ex Vivo Expansion Model

“…þ T cells were obtained by positive selection from mononuclear cells of human peripheral blood as previously described [21,22]. The purity of CD8 þ cells was assessed by flow cytometry and was routinely more than 98% (data not shown).…”

“…Samples of fresh (preculture) and cultured CD8 þ cells were stained using fluorescent-labelled monoclonal antibodies CD45RA, CD45RO, CD8 and CD57 to confirm their immunophenotype. All antibody staining steps were performed at 4 C for 30 min as described previously [21,22]. Appropriate isotype controls were also performed for each marker.…”

“…For the removal of glycosaminoglycans, bovine serum albumin/PBS solution containing either 10 U/ml heparinase II or chondroitinase ABC 10 U/ml was incubated with cultured cells at the indicated time points for 1.5 h at 24 C [26]. Following the incubation period with sodium chlorate and glycosaminoglycan lyses, cells were washed twice with PBS and cultured as described previously [21,22] in the presence of different PS-ODNs.…”