Polyclonal CD8+/CD57+ T cell expansions: Clinical significance

Polyclonal CD8(+)/CD57(+) T cell lymphocytosis can be observed in various conditions such as chronic viral infections, autoimmune cytopenias, connective tissue diseases, chronic graft-versus-host disease and primary or secondary immune deficiencies. This population results from the chronic stimulation of CD8(+)/CD28(+)/CD57(-) lymphocytes by exogenous (mostly infection-related), autologous or allogeneic antigens. Paralleling chronic antigen stimulation, these CD8(+) T cells acquire a poor capacity to proliferate in standard conditions in relation with the loss of CD28, whereas CD57 antigen becomes expressed at their surface. CD8(+)/CD57(+) T cells represent activated cytotoxic T lymphocytes at a terminal stage of their differentiation with evidence of immunological senescence, which have usually lost their cytotoxic properties to become "regulatory" T cells. Patients with a CD8(+)/CD57(+) T cell lymphocytes expansion can display features of organ infiltration, as well as chronic idiopathic neutropenia. The search of this population has therefore a diagnostic value in clinical practice. A CD8(+)/CD57(+) T cell lymphocytes expansion must be suggested in patients with an organomegaly or organ(s) infiltration, particularly in patients infected by the human immunodeficiency virus or in the setting of allogeneic hematopoietic stem cell transplantation, as well as in patients with a neutropenia of unexplained origin. The identification of a CD8(+)/CD57(+) T cell lymphocytes expansion also has therapeutical consequences since patients with an organ infiltration or a neutropenia may respond remarkably to immunomodulatory therapies. The search of a CD8(+)/CD57(+) T cell expansion thus represents a useful and still poorly known diagnostic tool which clinical interest deserves further evaluation.