CD8+ CD28− and CD8+ CD57+ T cells and their role in health and disease

Abstract

Summary Chronic antigenic stimulation leads to gradual accumulation of late‐differentiated, antigen‐specific, oligoclonal T cells, particularly within the CD8+ T‐cell compartment. They are characterized by critically shortened telomeres, loss of CD28 and/or gain of CD57 expression and are defined as either CD8+CD28− or CD8+CD57+ T lymphocytes. There is growing evidence that the CD8+CD28− (CD8+CD57+) T‐cell population plays a significant role in various diseases or conditions, associated with chronic immune activation such as cancer, chronic intracellular infections, chronic alcoholism, some chronic pulmonary diseases, autoimmune diseases, allogeneic transplantation, as well as has a great influence on age‐related changes in the immune system status. CD8+CD28− (CD8+CD57+) T‐cell population is heterogeneous and composed of various functionally competing (cytotoxic and immunosuppressive) subsets thus the overall effect of CD8+CD28− (CD8+CD57+) T‐cell‐mediated immunity depends on the predominance of a particular subset. Many articles claim that CD8+CD28− (CD8+CD57+) T cells have lost their proliferative capacity during process of replicative senescence triggered by repeated antigenic stimulation. However recent data indicate that CD8+CD28− (CD8+CD57+) T cells can transiently up‐regulate telomerase activity and proliferate under certain stimulation conditions. Similarly, conflicting data is provided regarding CD8+CD28− (CD8+CD57+) T‐cell sensitivity to apoptosis, finally leading to the conclusion that this T‐cell population is also heterogeneous in terms of its apoptotic potential. This review provides a comprehensive approach to the CD8+CD28− (CD8+CD57+) T‐cell population: we describe in detail its origins, molecular and functional characteristics, subsets, role in various diseases or conditions, associated with persistent antigenic stimulation.

Cytomegalovirus‐Productive Infection Is Associated With Acute Coronary Syndrome

“…Whatever the actual trigger of the inflammatory process in atherosclerosis, it is associated with perturbation of the T cell repertoire in blood and in plaques 41. In particular, the expansion of unusual T lymphocytes in peripheral blood (CD4 + CD28 − T cells) is strongly associated with the recurrence of acute coronary events42 and appears in other diseases,43 such as acute ischemic stroke 44. In contrast, accumulation of intermediately and late‐differentiated CD8 Tem cells in blood is associated with CMV infection 45, 46, 47…”

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

“…Although we did not find preferential activation of CD8 + CD57 + T cells in our in vitro EBV infections, this population, already at high frequencies in CMV + children, increased further in EBV-infected cultures and upon coculture with EBV + LCL (but not with the EBV 2 cell line Ramos). The increase in frequency could result from preferential survival/maintenance of this population as opposed to CD8 + CD57 2 T cells, upregulation of CD57 on CD57 2 cells, something that normally occurs upon persistent antigenic stimulation (45), or through division of pre-existing CD57 + cells. Although CD57 has been associated with replicative senescence (46), these cells are able to divide under conditions where costimulatory factors are present (34).…”

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…It is believed that CD8 + CD57 + T cells are highly differentiated antigen‐driven effector cells in a state of replicative senescence with limited capacities to proliferate 88, 89, 90, 91, 92. Recent reports, however, suggest that these CD8 + CD57 + CD28 − T cells might comprise a rather heterogeneous group of highly antigen‐experienced cells that, depending on the immunobiological context and stimuli, differ in their susceptibility to apoptosis and their capability to proliferate and expand 84, 93, 94, 95…”