CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I–αβTCR interaction and become IL-10-producing active regulatory cells

Abstract

CD8(+)CD122(+) regulatory T cells (CD8(+)CD122(+) Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-gamma production of both CD8(+) and CD4(+) target cells. This study investigated the molecular mechanisms of the recognition of target cells by CD8(+)CD122(+) Treg using an in vitro culture system that reconstitutes the regulatory action of these cells. Naive CD8(+)CD122(+) Treg co-cultured with pre-activated T cells became active Treg that produced IL-10 and suppressed IFN-gamma production from the target T cells. CD8(+)CD122(+) Treg effectively suppressed the IFN-gamma production of the target cells of syngeneic mouse strains but not of allogeneic mouse strains with incompatible MHC. By using MHC-congeneic mouse strains, MHC-restricted suppression by CD8(+)CD122(+) Treg was further confirmed. The blockade of cell surface molecules either on the Treg or on the target cells by specific blocking antibodies indicated that H-2K, H-2D, alphabetaTCR and CD8 were involved in the regulatory action but I-A and Qa-1 were not. These results indicate that CD8(+)CD122(+) Treg recognize already-activated T cells via the interaction of conventional MHC class I-alphabetaTCR and become active regulatory cells that produce IL-10 and suppress the target cells.

CD8 + CD122 + CD49d low regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity

“…Another important molecular interaction is that of MHC class I and TCR. β2-microglobulin-deficient cells are neither regulated in the previous study (33) nor in the present study, suggesting the importance of specific recognition between "the regulatory cells" and "the regulated cells." Another important molecule involved in the action of CD8 + Tregs might be Qa-1, a nonclassical MHC class I molecule (MHC-Ib), as H. Cantor and his colleague found and reported a CD8 + T-cell subset that showed a regulatory activity under a Qa-1-restricted manner (30).…”

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

“…10 The CD8 1 Tregs also recognized activated T cells via the interaction of MHC class I-ab TCR and regulated target T cells by producing IL-10. 44 We also found that suppression of allograft rejection by IL-10-deficient CD8 1 CD122 1 Tregs was significantly reduced. 18 However, IL-10 did not account for all mechanisms underlying CD8 1 CD122 1 Treg suppression.…”

“…As shown in Figure 2, IL-10 produced by CD8 1 CD122 1 Tregs appears to be a main mechanism responsible for their suppression. 10,18,44 Endharti et al 10 presented the first data showing that CD8 1 CD122 1 Tregs suppressed IFN-c production and proliferation of CD8 1 T cells by producing IL-10 in vitro. 10 The CD8 1 Tregs also recognized activated T cells via the interaction of MHC class I-ab TCR and regulated target T cells by producing IL-10.…”

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

“…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). Moreover, CD8 + CD122 + Tregs can maintain homeostasis of CD8 + T cells by controlling CD8 + T cell activation in vivo and in vitro, mirrored by dampened IFN-γ production and suppression of CD8 + CD122 lo T cell proliferation (45,78). In addition, CD8 + T cells with regulatory functions have been shown to suppress activated CD4 + T cells (44).…”