CD8
            <sup>+</sup>
            T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice

Kim, Hye-Jung; Wang, Xuan; Radfar, Soroosh; Sproule, Thomas J.; Roopenian, Derry C.; Cantor, Harvey

doi:10.1073/pnas.1018974108

Cited by 149 publications

(205 citation statements)

References 35 publications

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“…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.…”

Section: Introductionmentioning

confidence: 87%

“…14 The development of systemic lupus erythematosus-like disease in B6-Yaa mutant mice was associated with a defect in CD8 1 CD122 1 Treg cell activity, indicating that this Treg subset represents an effective therapeutic approach to systemic lupus erythematosus-like autoimmune disease. 16 Taken together, CD8 1 CD122 1 Tregs play an important role in the suppression or prevention of various autoimmune diseases in experimental animal models. Recent studies have also shown that CD8 1 CD122 1 Tregs play a regulatory role in alloimmunity as well as tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Xie²,

Zeng

et al. 2014

Cell Mol Immunol

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Despite extensive studies on CD4 1 CD25 1 regulatory T cells (Tregs) during the past decade, the progress on their clinical translation remains stagnant. Mounting evidence suggests that naturally occurring CD8 1 CD122 1 T cells are also Tregs with the capacity to inhibit T-cell responses and suppress autoimmunity as well as alloimmunity. In fact, they are memory-like Tregs that resemble a central memory T cell (T CM ) phenotype. The mechanisms underlying their suppression are still not well understood, although they may include IL-10 production. We have recently demonstrated that programmed death-1 (PD-1) expression distinguishes between regulatory and memory CD8 1 CD122 1 T cells and that CD8 1 CD122 1 Tregs undergo faster homeostatic proliferation and are more potent in the suppression of allograft rejection than conventional CD4 1 CD25 1 Tregs. These findings may open a new line of investigation for accelerating effective Treg therapies in the clinic. In this review, we summarize the significant progress in this promising field of CD8 1 CD122 1 Treg research and discuss their phenotypes, suppressive roles in autoimmunity and alloimmunity, functional requirements, mechanisms of action and potential applications in the clinic.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Xie²,

Zeng

et al. 2014

Cell Mol Immunol

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“…However, MHC‐E can also present some peptides derived from autoantigens and pathogens, which are recognized by CD8 + T cells. Qa‐1 is expressed at high levels on GC CXCR5 + CD4 + cells, while CXCR5 − CD4 + T cells express very low levels of Qa‐1; hence, Qa‐1‐restricted CXCR5 + CD8 + T cells specifically target CXCR5 + Tfh cells 254. By mediating perforin‐dependent lysis of GC Tfh cells, they reduce the GC response and help to prevent autoantibody development 252, 254, 255.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

“…Qa‐1 is expressed at high levels on GC CXCR5 + CD4 + cells, while CXCR5 − CD4 + T cells express very low levels of Qa‐1; hence, Qa‐1‐restricted CXCR5 + CD8 + T cells specifically target CXCR5 + Tfh cells 254. By mediating perforin‐dependent lysis of GC Tfh cells, they reduce the GC response and help to prevent autoantibody development 252, 254, 255. Although Qa‐1‐restricted CD8 + Treg cells express CXCR5, they do not express ICOS or PD‐1 or markers characteristic of CD4 + Treg cells such as FoxP3.…”

Section: Regulatory Cell Populations and Their Relationship To Bnab Imentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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“…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). In their recent publications, however, the Qa-1-restricted CD8 + Tregs they proposed were apparently shown to be CD122 + CD44 + (34,35). The Qa-1-restricted CD8 + Treg is overlapped with or involved in the CD8 +…”

Section: Cd122mentioning

confidence: 99%

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

Akane

Kojima

Mak

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The Fas/FasL (CD95/CD178) system is required for immune regulation; however, it is unclear in which cells, when, and where Fas/FasL molecules act in the immune system. We found that CD8+CD122+ cells, which are mostly composed of memory T cells in comparison with naïve cells in the CD8+CD122− population, were previously shown to include cells with regulatory activity and could be separated into CD49dlow cells and CD49dhigh cells. We established in vitro and in vivo experimental systems to evaluate the regulatory activity of CD122+ cells. Regulatory activity was observed in CD8+CD122+CD49dlow but not in CD8+CD122+CD49dhigh cells, indicating that the regulatory cells in the CD8+CD122+ population could be narrowed down to CD49dlow cells. CD8+CD122− cells taken from lymphoproliferation (lpr) mice were resistant to regulation by normal CD122+ Tregs. CD122+ Tregs taken from generalized lymphoproliferative disease (gld) mice did not regulate wild-type CD8+CD122− cells, indicating that the regulation by CD122+ Tregs is Fas/FasL-dependent. CD122+ Tregs taken from IL-10–deficient mice could regulate CD8+CD122− cells as equally as wild-type CD122+ Tregs both in vitro and in vivo. MHC class I-missing T cells were not regulated by CD122+ Tregs in vitro. CD122+ Tregs also regulated CD4+ cells in a Fas/FasL-dependent manner in vitro. These results suggest an essential role of Fas/FasL as a terminal effector of the CD122+ Tregs that kill activated T cells to maintain immune homeostasis.

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CD8 ⁺ T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice

Cited by 149 publications

References 35 publications

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

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

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

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

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CD8 + T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice

Cited by 149 publications

References 35 publications

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

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

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

CD8+CD122+CD49dlowregulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity

Contact Info

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Resources

About

CD8 ⁺ T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice

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