Faculty Opinions recommendation of Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells.

2003 ◽  
Author(s):  
Leo Lefrancois
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Memory Cells ◽  
Interleukin 7

Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells

10.1038/ni946 ◽  
2003 ◽  
Vol 4 (7) ◽  
pp. 680-686 ◽  
Author(s):  
Benedict Seddon ◽  
Peter Tomlinson ◽  
Rose Zamoyska
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Memory Cells ◽  
Interleukin 7

Effects of exogenous interleukin-7 on human thymus function

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2851-2858 ◽  
Author(s):  
Yukari Okamoto ◽  
Daniel C. Douek ◽  
Richard D. McFarland ◽  
Richard A. Koup
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
De Novo ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Receptor ◽  
Cellular Division ◽  
Hematopoietic Stem ◽  
Human Thymus ◽  
Interleukin 7

Abstract Immune reconstitution is a critical component of recovery after treatment of human immunodeficiency virus (HIV) infection, cancer chemotherapy, and hematopoietic stem cell transplantation. The ability to enhance T-cell production would benefit such treatment. We examined the effects of exogenous interleukin-7 (IL-7) on apoptosis, proliferation, and the generation of T-cell receptor rearrangement excision circles (TRECs) in human thymus. Quantitative polymerase chain reaction demonstrated that the highest level of TRECs (14 692 copies/10 000 cells) was present in the CD1a+CD3−CD4+CD8+stage in native thymus, suggesting that TREC generation occurred following the cellular division in this subpopulation. In a thymic organ culture system, exogenous IL-7 increased the TREC frequency in fetal as well as infant thymus, indicating increased T-cell receptor (TCR) rearrangement. Although this increase could be due to the effect of IL-7 to increase thymocyte proliferation and decrease apoptosis of immature CD3− cells, the in vivo experiments using NOD/LtSz-scid mice given transplants of human fetal thymus and liver suggested that IL-7 can also directly enhance TREC generation. Our results provide compelling evidence that IL-7 has a direct effect on increasing TCR-αβ rearrangement and indicate the potential use of IL-7 for enhancing de novo naı̈ve T-cell generation in immunocompromised patients.

scholarly journals Interleukin-7 Enhances Proliferation Responses to T-Cell Receptor Stimulation in Naïve CD4+ T Cells from Human Immunodeficiency Virus-Infected Persons

2007 ◽  
Vol 81 (22) ◽  
pp. 12670-12674 ◽  
Author(s):  
Douglas A. Bazdar ◽  
Scott F. Sieg
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Healthy Controls ◽  
Receptor Stimulation ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Antigen Presenting

ABSTRACT Proliferation responses of naïve CD4+ T cells to T-cell receptor and interleukin-7 (IL-7) stimulation were evaluated by using cells from human immunodeficiency virus-positive (HIV+) donors. IL-7 enhanced responses to T-cell receptor stimulation, and the magnitude of this enhancement was similar in cells from healthy controls and from HIV+ subjects. The overall response to T-cell receptor stimulation alone or in combination with IL-7, however, was diminished among viremic HIV+ donors and occurred independent of antigen-presenting cells. Frequencies of CD127+ cells were related to the magnitudes of proliferation enhancement that were mediated by IL-7. Thus, IL-7 enhances but does not fully restore the function of naïve CD4+ T cells from HIV-infected persons.

scholarly journals Interleukin 7 Receptor Control of  T Cell Receptor γ Gene Rearrangement: Role of Receptor-associated Chains and Locus Accessibility

1998 ◽  
Vol 188 (12) ◽  
pp. 2233-2241 ◽  
Author(s):  
Scott K. Durum ◽  
Serge Candèias ◽  
Hiroshi Nakajima ◽  
Warren J. Leonard ◽  
Allison M. Baird ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
T Cell Receptor ◽  
Dna Cleavage ◽  
Gene Rearrangement ◽  
Trichostatin A ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Janus Kinase ◽  
Interleukin 7

VDJ recombination of T cell receptor and immunoglobulin loci occurs in immature lymphoid cells. Although the molecular mechanisms of DNA cleavage and ligation have become more clear, it is not understood what controls which target loci undergo rearrangement. In interleukin 7 receptor (IL-7R)α−/− murine thymocytes, it has been shown that rearrangement of the T cell receptor (TCR)-γ locus is virtually abrogated, whereas other rearranging loci are less severely affected. By examining different strains of mice with targeted mutations, we now observe that the signaling pathway leading from IL-7Rα to rearrangement of the TCR-γ locus requires the γc receptor chain and the γc-associated Janus kinase Jak3. Production of sterile transcripts from the TCR-γ locus, a process that generally precedes rearrangement of a locus, was greatly repressed in IL-7Rα−/− thymocytes. The repressed transcription was not due to a lack in transcription factors since the three transcription factors known to regulate this locus were readily detected in IL-7Rα−/− thymocytes. Instead, the TCR-γ locus was shown to be methylated in IL-7Rα−/− thymocytes. Treatment of IL-7Rα−/− precursor T cells with the specific histone deacetylase inhibitor trichostatin A released the block of TCR-γ gene rearrangement. This data supports the model that IL-7R promotes TCR-γ gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus.

Interleukin 7 preferentially supports the growth of γδ T cell receptor-bearing T cells from fetal thymocytes in vitro

1991 ◽  
Vol 3 (11) ◽  
pp. 1067-1075 ◽  
Author(s):  
Yoshihiro Watanabe ◽  
Tetsuo Sudo ◽  
Nagahiro Minato ◽  
Akio Ohnishi ◽  
Yoshimoto Katsura
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Γδ T Cell ◽  
Interleukin 7 ◽  
Γδ T Cell Receptor

scholarly journals Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene

Science ◽  
1993 ◽  
Vol 261 (5117) ◽  
pp. 93-95 ◽  
Author(s):  
K Muegge ◽  
M. Vila ◽  
S. Durum
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Interleukin 7 ◽  
T Cell Receptor Beta ◽  
Beta Gene ◽  
Receptor Beta

scholarly journals Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

2001 ◽  
Vol 193 (6) ◽  
pp. 689-698 ◽  
Author(s):  
Joonsoo Kang ◽  
Ariane Volkmann ◽  
David H. Raulet
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Fate ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Developmental Potential ◽  
Cd8 Cells ◽  
Interleukin 7

Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.

A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor α chain-deficient mice

1997 ◽  
Vol 27 (1) ◽  
pp. 100-104 ◽  
Author(s):  
Tessa Crompton ◽  
Susan V. Outram ◽  
Jennifer Buckland ◽  
Michael J. Owen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Interleukin 7 ◽  
Α Chain ◽  
Thymocyte Differentiation ◽  
Deficient Mice

scholarly journals Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.

2022 ◽  
Author(s):  
Rayner M. L. Queiroz ◽  
Siân Piper ◽  
Johanna Susan Rees ◽  
Sam Strickson ◽  
Emmanuel Briend ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Phosphorylation Site ◽  
Cell Receptor ◽  
Interacting Protein ◽  
Interleukin 7 ◽  
Signal Transduction Proteins ◽  
Cellular Immune

The ability of the cellular immune system to discriminate self from foreign antigens depends on the appropriate calibration of the T-cell receptor (TCR) signalling threshold. The lymphocyte homeostatic cytokine interleukin 7 (IL-7) is known to affect TCR thresholding, but the molecular mechanism is not fully elucidated. A better understanding of this process is highly relevant in the context of autoimmune disease therapy and cancer immunotherapy. We sought to characterise the early signalling events attributable to IL-7 priming; in particular, the altered phosphorylation of signal transduction proteins and their molecular localisation to the TCR. By integrating high-resolution proximity- phospho-proteomic and imaging approaches using primary T cells, rather than engineered cell lines or an in vitro expanded T cell population, we uncovered transduction events previously not linked to IL-7. We show that IL-7 leads to dephosphorylation of cytohesin interacting protein (CYTIP) at a hitherto undescribed phosphorylation site (pThr280) and alters the co-localisation of cytohesin 1 with the TCR and LFA-1 integrin. These results show that IL-7, acting via CYTIP and cytohesin-1, may impact TCR activation thresholds by enhancing the co-clustering of TCR and LFA-1 integrin.

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