Bystander Central Memory but Not Effector Memory CD8+ T Cells Suppress Allograft Rejection

Ni, Wan; Dai, Hehua; Wang, Tao; Moore, Yolonda; Zheng, Xin Xiao; Dai, Zhenhua

doi:10.4049/jimmunol.180.1.113

Cited by 35 publications

(38 citation statements)

References 55 publications

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“…In rats, a regulatory CD8 + Foxp3 + CTLA4 + CD45RC lo population has been described; however, controversy exists as to whether these cells suppress via production of cytokines or cell-to-cell contact (42,75). Reports that CD8 + T cells can suppress through TGF-β also exist (48,76). In contrast to these reports, we now describe an IFN-γ-dependent mechanism of CD8 + CCR7 + T cell-mediated immunosuppression in the murine lung.…”

Section: Discussioncontrasting

confidence: 44%

“…While the vast majority of studies suggest that memory T lymphocytes potentiate alloimmune responses and inhibit tolerance induction (46,47), it is possible that certain subsets of these cells may suppress alloreactivity (48). It is noteworthy that CD8 + T lymphocytes, including memory CD8 + T cells, were present in the lung at baseline, even in the absence of acute inflammation or alloantigen stimulation ( Figure 6A).…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Krupnick¹,

Lin²,

Li³

et al. 2014

J. Clin. Invest.

115

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Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade-mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8 + T cells (CD44 hi CD62L hi CCR7 + ). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts.

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Section: Discussioncontrasting

confidence: 44%

Section: Introductionmentioning

confidence: 90%

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Krupnick¹,

Lin²,

Li³

et al. 2014

J. Clin. Invest.

115

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show abstract

“…We have previously shown that 'bystander' memory CD8 1 T cells with a central memory T cell (T CM ) phenotype suppress allograft rejection. 37 We also have found that the suppressive capacity of CD8 1 CD122 1 Tregs is partially dependent on IL-10 and that their suppression in vitro is donor-nonspecific. 18 Our findings suggest that the suppression mediated by naturally occurring CD8 1 CD122 1 Tregs is not antigen-specific.…”

Section: Introductionmentioning

confidence: 84%

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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“…We observed the CD25 − CD8 + expansion in the lung occurred primarily in the CD44 high effector/memory compartment. While it has been shown that naive T cells may undergo bystander proliferation [18,44], the majority of studies report that, after infection, antigen non-specific proliferation occurs in the effector/memory compartment [14,19,[51][52][53]. CD44 high CD8…”

Section: Discussionmentioning

confidence: 99%

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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Summary Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8 + T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8 + T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44 high CD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbuminspecific (OT-I) CD8 + T cells, which are not specific to influenza. These nonspecific CD8 + T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8 + T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8 + T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

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Bystander Central Memory but Not Effector Memory CD8+ T Cells Suppress Allograft Rejection

Cited by 35 publications

References 55 publications

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

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

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

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