Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo

Schluns, Kimberly S.; Kieper, William C.; Jameson, Stephen C.; Lefrançois, Leo

doi:10.1038/80868

Cited by 1,448 publications

(1,450 citation statements)

References 59 publications

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“…1). A number of different cytokines, particularly IL-7 and IL-15, have been reported to be required for survival and maintenance of memory T cells in vivo [26,27,29,30]. In our model system, IL-2 is the only exogenously added cytokine.…”

Section: Discussionmentioning

confidence: 99%

“…It has become evident that IL-15 controls both homeostatic proliferation and survival of CD8 memory cells in vivo [26,27], possibly by mimicking a TCR response [28]. In addition, IL-7 was also shown to promote homeostatic proliferation in CD8 T cells [29]. Recently, it has been shown that IL-7, but not IL-15, is required for the maintenance of CD4 memory T cells [27,30].…”

Section: Introductionmentioning

confidence: 99%

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In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

et al. 2006

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An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These longterm cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl-x L and Bcl-2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

et al. 2006

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“…Studies that examine mice deficient in IL-7 or IL-15 have demonstrated that these cytokines have a supportive role in the survival and/or proliferation of adoptively transferred T cells in lymphodepleted hosts [36][37][38][39][40]. The absence of IL-7 inhibits naïve CD4 + and CD8 + T-cell homeostatic proliferation and survival in a lymphopenic environment.…”

Section: Evidence For the Presence Of Homeostatic Cellular Cytokine 'mentioning

confidence: 99%

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

404

288

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Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine 'sinks' for homeostatic γ C -cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4 + CD25 + regulatory T (Treg) cells that suppress tumorreactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigenpresenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.

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“…8 IL-7 binds to the dimerized receptors of IL-7 receptor-a (IL-7Ra) (CD127) and the g-chain receptor (CD132) to exert its effect. The IL-7Ra is also found in soluble (s) form, as sIL-7Ra in plasma, and is produced as a result of splicing exon-6 from the IL-7Ra gene mRNA.…”

Section: Introductionmentioning

confidence: 99%

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

et al. 2011

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We previously found an association between faster CD4 þ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-a (IL-7Ra) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n ¼ 352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7Ra single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n ¼ 57). Soluble (s)IL-7Ra levels were measured by ELISA. In UARTO, IL-7Ra haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P ¼ 0.020) and no association was found with LMM (P ¼ 0.958). The tagging-SNP for IL-7Ra haplotype-2 (rs6897932) was associated with decreased sIL-7Ra (Po0.001). The haplotypes for the IL-7Ra were significantly different in Africans and Caucasians. Using IL-7Ra genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P ¼ 0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P ¼ 0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7Ra haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7Ra SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.

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Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo

Cited by 1,448 publications

References 59 publications

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

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