The frequency of regulatory CD3+CD8+CD28−CD25+ T lymphocytes in human peripheral blood increases with age

Abstract

Aging is commonly associated with immune deficiency and dysregulation. The aging of the immune system involves a progressive reduction in naïve T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. We have investigated frequency, phenotype, and function of CD3+CD8+CD28(-)CD25+ T cells in healthy volunteers over a wide age range. We demonstrate that the frequency of CD3+CD8+CD28(-)CD25+ T cells in healthy volunteers increases with age. Peripheral CD3+CD8+CD28(-)CD25+ T cells share phenotypic and functional features with CD3+CD4+CD25+ regulatory T cells (Tregs): In particular, they strongly express CTLA-4 and forkhead box P3. We observed that in vitro, functional titration assays of CD3+CD8+CD28(-)CD25+ T cells show equivalent regulatory function in young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. Finally, CD3+CD8+CD28(-)CD25+ T cells seem to specifically express the CD122 receptor. Altogether, these observations demonstrate an increase in peripheral blood CD8+ Tregs associated with aging.

Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-ResistantMycobacterium tuberculosisM and Ra Strains

“…This difference may be ascribed to the fact that MDR-TB patients constituted a much more heterogeneous population in terms of previous duration of disease and anti-TB treatment. Recently, CD8 ϩ Treg cells that are able to inhibit T-cell proliferation and cytokine production have also been described, and human CD8 ϩ CD25 ϩ Foxp3 ϩ cells have been observed in adult PBMC and in neonatal thymus (8,52). In line with this, we detected an increased percentage of CD8 ϩ CD25 ϩ Foxp3 ϩ cells only in MDR-TB patients (Table 1).…”

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

“…On the other hand, we failed to demonstrate a significant modification in CD8+ CD28-Treg cells [22,34]. However, this latter subset has been found reduced in immune-driven diseases such as type-1 juvenile diabetes mellitus and systemic lupus erythematosus affecting predominantly young people [22,34]; the age of the patients can play a role in this phenomenon as it is known that the CD8+ CD28-subset increases with age [12,30] and BP affects predominantly elderly people (74 years median age in this study). The CD25bright expression does not exclusively identifies this T-cell population as it can be found also on activated T cells and APC [10,19], whilst FOXP3 is the most exclusive Treg marker as the inhibitory properties lies in the FOXP3+ subset [10,18,20,32,33].…”

CD8+Foxp3+ T cells in peripheral blood of relapsing-remitting multiple sclerosis patients

“…Besides CD4 ϩ Treg, CD8 ϩ Treg expressing Foxp3 also seem to contribute to the suppression of antiviral and antitumoral immune response. Peripheral blood CD8 ϩ CD25 ϩ Foxp3 ϩ T cells that share phenotypic and functional features with CD4 ϩ CD25 ϩ Foxp3 ϩ T cells [5,6,25] and increase with age [25] have been identified in low amount ex vivo in humans but they may be recruited to the cancer tissue or to the sites of inflammation where they suppress antigen-specific immune response [5,6]. Increased percentage of CD8 ϩ CD25 ϩ Foxp3 ϩ T cells able to suppress CD4 ϩ CD25 Ϫ T cells proliferation and cytokine production have been found in peripheral blood and in tumor tissue from patients with colorectal cancer [5] and in prostate cancer specimens [7].…”