IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells

Li, JiChu; Huston, Gail E.; Swain, Susan L.

doi:10.1084/jem.20030725

Cited by 285 publications

(271 citation statements)

References 43 publications

Supporting

Mentioning

254

Contrasting

Order By: Relevance

“…IL-7Ra has recently been shown to mediate the survival of previously activated T cells in vivo [22,29,30]. We therefore examined the expression of IL-7Ra on activated DO11.10 T cells freshly harvested from adoptive transfer recipients, hypothesizing that its expression would be higher in the cells from TLR agonist-treated mice.…”

Section: Il-7ra Expression Is Not Increased By Tlr Agonistsmentioning

confidence: 99%

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

et al. 2005

View full text Add to dashboard Cite

Immunological adjuvants increase the clonal burst size of antigen-specific T cell populations by mechanisms that remain incompletely understood. Using the DO11.10 adoptive transfer system to study peptide-stimulated T cell responses, we found that TLR agonist treatment increased the extent of cellular division undergone by responding T cells, but not by enough to explain the net increases in T cell yield that were achieved. Two novel analyses involving CFSE dye dilution analysis were used to characterize the shortfall, both of which were consistent with the idea that DO11.10 T cells are frequently lost during proliferation unless TLR agonists are present. T cell loss during clonal expansion was correlated with decreased levels of Bcl-2, but TLR agonists did not appear to afford protection by restoring levels of Bcl-2 or of cell surface IL-7Ra chain expression. TLR-mediated protection also failed to correlate with increased expression of Bcl-x or decreased expression of pro-apoptotic Bim. Our findings suggest that DO11.10 T cells stimulated by antigenic peptide in vivo divide well, but fail to accumulate efficiently unless TLR agonists are present.

show abstract

Section: Il-7ra Expression Is Not Increased By Tlr Agonistsmentioning

confidence: 99%

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

et al. 2005

View full text Add to dashboard Cite

show abstract

“…IL-7 regulates peripheral T-cell homeostasis, and contributes to the generation and long-term survival of both CD4 1 and CD8 1 memory T lymphocytes in vivo [30,31]. In some cases IL-7 amplifies Agdriven T-cell responses [32][33][34][35][36], favors the transition of effector to memory cells [31,[37][38][39], and sustains a slow, homeostaticlike, Ag-independent memory T-cell proliferation [24,30,40]. Furthermore, its administration at the time of Ag withdrawal supports memory CD8 1 T-cell generation [41], and enhances vaccine-mediated immunity when provided in adjuvant settings [42,43].…”

Section: Introductionmentioning

confidence: 99%

IL‐7 is superior to IL‐2 for ex vivo expansion of tumour‐specific CD4⁺ T cells

Caserta

Alessi²,

Basso³

et al. 2010

Eur J Immunol

View full text Add to dashboard Cite

It is well established that tumours hinder both natural and vaccine-induced tumourspecific CD4 1 T-cell responses. Adoptive T-cell therapy has the potential to circumvent functional tolerance and enhance anti-tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8 1 T cells are currently available, data on tumour-specific CD4 1 T cells remain scarce. We report here that CD4 1 T cells sensitized to tumour-associated Ag in vivo, proliferate in vitro in response to IL-7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory-like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumoursensitized T cells among other memory and naive lymphocytes following exposure to IL-7. Also IL-2, previously used to expand anti-tumour CTL, promotes tumour-specific CD4 1 T-cell accumulation. However, IL-7 is superior to IL-2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties, that are required by helper CD4 1 T cells to confer therapeutic efficacy upon transplantation in tumour-bearing hosts. Together our data support a unique role for IL-7 in retrieving memory-like CD4 1 T cells suitable for adoptive T-cell therapy.Key words: Adoptive T-cell therapy . Cytokines . T helper cells . Tumour immunology Supporting Information available online IntroductionAdoptive cell therapy (ACT) with tumour-specific CD8 1 T lymphocytes has become one of the most promising approaches in cancer therapy. Rosenberg et al. first demonstrated the possibility to expand tumour-specific cytotoxic CD8 1 lymphocytes (CTL) from tumour lesions in high doses of IL-2 [1]. These authors later showed that the state of lymphocyte differentiation, induced in the presence of common g-chain receptor cytokines, is critical for therapeutic efficacy [2,3]. In spite of the recognized importance of Ag-specific CD4 1 T cells in both adaptive and innate immune responses, their identification remains elusive, and their in vitro amplification is hindered by the absence of reliable protocols able to support cell proliferation in the absence of terminal differentiation. While, Ag tumours elicit natural tumour-specific CD4 1 T-cell responses [4][5][6][7][8][9][10], functional tolerance is eventually observed through the induction of T-cell anergy [11,12], T-cell depletion [13] or the limitation of the memory repertoire [10,14,15]. This is possibly due to Ag persistence, and continual TCR signaling, as in the case of chronic 470viral infections [16][17][18]. In addition, regulatory CD4 1 T cells have been frequently found in the case of tumours, often among the tumour-infiltrating lymphocytes, thereby persuading the general interest towards CD8 1 CTL. Thus, CD4 1 T cells have not been widely exploited in ACT as well as the properties (i.e. homing potential, functionality, and survival) that CD4 1 T cells might require for successful applications in ACT are much less known than in the case for CD8 1 CTL.A large, still not definitive, amount of ...

show abstract

“…Other reports have demonstrated an important function for IL7 in the generation of CD4 þ memory cells as well. 10 Basal levels of IL7 are sufficient to maintain survival of the CD8 þ memory pool and may contribute to the survival of the CD4 þ memory pool. 11 Interestingly, IL7R signaling has an immunomodulatory role in dendritic cells, especially in the context of thymic stromal lymphopoietin (TSLP), which also signals through the IL7Ra in a heterodimeric complex by dimerization with the product of the cytokine receptor-like factor 2 gene (CRLF2) to form the TSLP receptor.…”

Section: Introductionmentioning

confidence: 99%

Variation in IL7R predisposes to sarcoid inflammation

et al. 2009

View full text Add to dashboard Cite

Sarcoidosis is a chronic granulomatous disorder characterized by a massive influx of Th1 lymphocytes. Both naive and memory T cells express high levels of interleukin 7 receptor-a (IL7Ra), encoded by the IL7R gene. The purpose of this study was to investigate the role of the IL7R gene region in susceptibility to sarcoidosis. Six common single-nucleotide polymorphisms (SNPs) spanning IL7R were genotyped and analyzed in 475 sarcoidosis patients and 465 healthy controls. Replication of one significant associated SNP was carried out in 206 independent sarcoidosis patients, 127 controls and 126 patients with Lö fgren's disease. The rs10213865 SNP was associated with sarcoidosis (P ¼ 0.008), and in silico analysis showed a complete linkage (r 2 ¼ 1, D 0 ¼ 1) with a functional nonsynonymous coding SNP in exon 6 (rs6897932, T244I). Combined analysis of 663 individuals with sarcoidosis and 586 controls (homozygous carriers of risk allele, P ¼ 5 Â 10 À4 , odds ratio ¼ 1.49 (1.19-1.86)) provided strong statistical support for a genuine association of IL7R with the risk of sarcoidosis. In addition, we report the same trend between variation in the IL7R gene and patients with Lö fgren's disease, suggesting that variation in IL7R may confer general risk for developing granulomatous lung disease.

show abstract

IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells

Cited by 285 publications

References 43 publications

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

IL‐7 is superior to IL‐2 for ex vivo expansion of tumour‐specific CD4⁺ T cells

Variation in IL7R predisposes to sarcoid inflammation

Contact Info

Product

Resources

About

IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells

Cited by 285 publications

References 43 publications

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment

IL‐7 is superior to IL‐2 for ex vivo expansion of tumour‐specific CD4+ T cells

Variation in IL7R predisposes to sarcoid inflammation

Contact Info

Product

Resources

About

IL‐7 is superior to IL‐2 for ex vivo expansion of tumour‐specific CD4⁺ T cells