Cutting Edge: Programmed Death-1 Defines CD8+CD122+ T Cells as Regulatory versus Memory T Cells

Abstract

Recent convincing data have shown that naturally occurring CD8+CD122+ T cells are also regulatory T cells. Paradoxically, CD8+CD122+ T cells have been well described as memory T cells. Given their critical role in tolerance versus long-term immunity, it is important to reconcile this profound dichotomy. In this study, we reported that CD8+CD122+ T cells contain both programmed death-1 (PD-1)− and PD-1+ populations. It was CD8+CD122+PD-1+ T cells, but not their PD-1− counterparts, that suppressed T cell responses in vitro and in vivo. This suppression was largely dependent on their production of IL-10. Moreover, the costimulatory signaling of both CD28 and PD-1 is required for their optimal IL-10 production. In contrast, Ag-specific CD8+CD122+PD-1− T cells were bona fide memory T cells. Thus, CD8+CD122+ T cells can be either regulatory T or memory T cells, depending on their PD-1 expression and Ag specificity. This study reconciles previously contradictory findings and has important implications for tolerance induction.

Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

“…In a number of experimental models in mice, CD8 + CD122 + T cells have been shown to be indispensable for sustaining immune homeostasis, including the induction of tolerance or suppression of autoimmunity (44,45,76,77). Insights arising from Cd122 -/-mouse studies support the functional role of this marker in maintaining immune homeostasis, as Cd122 -/-mice spontaneously develop severe hyperimmunity (44,45,78,79).…”

A naturally occurring CD8+CD122+ T-cell subset as a memory-like Treg family

“…16,17 We have also found that CD8 1 CD122 1 T cells are memory-like Tregs that suppress allograft rejection in a murine model. 18 Hence, CD8 1 CD122 1 Tregs correspond to CD4 1 CD251 Tregs, given that CD122 is the b subunit of the IL-2 receptor on T cells, while CD25 is the a subunit of the same receptor, 19 which indicates that both subunits of the receptor are involved in Treg regulation. However, CD8 1 CD122 1 Tregs are recently emerging and relatively understudied in comparison with CD4 1 CD25 1 Tregs.…”

CD8+Foxp3+ T cells share developmental and phenotypic features with classical CD4+Foxp3+ regulatory T cells but lack potent suppressive activity

“…Certain surface phenotypes such as CD28 À [7], CD122 1 [8], CD8aa 1 [9,10], latencyassociated peptide (LAP) 1 [11] and restriction to the nonclassical MHCI molecule Qa-1 [12] have been linked with immunosuppressive functions of CD8 1 T cells. However, Foxp3 expression was either absent in these populations [8,9,[13][14][15], incongruent with the defining surface phenotype [11] or was not investigated specifically on a protein level [16]. Additionally, the isolation of viable CD8 1 Foxp3 1 populations was hampered by the nuclear localization of Foxp3 in conjunction with the occurrence of these cells at low numbers in nonmanipulated mice [2,17], rendering the identity and relevance of mouse CD8 1 Foxp3 1 T cells unclear.…”

“…Certain surface phenotypes such as CD28 À [7], CD122 1 [8], CD8aa 1 [9, 10], latencyassociated peptide (LAP) 1 [11] and restriction to the nonclassical MHCI molecule Qa-1 [12] have been linked with immunosuppressive functions of CD8 1 T cells. However, Foxp3 expression was either absent in these populations [8,9,[13][14][15] …”