Exogenous IL-7 increases recent thymic emigrants in peripheral lymphoid tissue without enhanced thymic function

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1110-1119 ◽  
Author(s):  
Yu-Waye Chu ◽  
Sarfraz A. Memon ◽  
Susan O. Sharrow ◽  
Frances T. Hakim ◽  
Michael Eckhaus ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Recent Thymic Emigrants ◽  
Short Term ◽  
Altered Expression ◽  
Thymic Function ◽  
Immune Organs ◽  
Interleukin 7 ◽  
Thymectomized Mice

AbstractInterleukin 7 (IL-7) is critical in maintaining thymic-dependent and thymic-independent pathways of T-cell homeostasis. T-cell receptor (TCR) rearrangement excision circles (TRECs) have been used as markers for recent thymic emigrants (RTEs) in assessing human thymic function. To study the thymic and peripheral effects of IL-7 on RTEs, we measured TREC content and peripheral naive T-cell subsets and turnover in IL-7-treated mice. Short-term administration of IL-7 into thymus-intact mice resulted in increased total TREC numbers, consistent with RTE accumulation. Decreases in TREC frequency were attributable to dilution secondary to increased cell turnover. Significantly, IL-7 administration into thymectomized mice resulted in patterns of decreased TREC frequency and increased total TREC number similar to those in IL-7-treated thymus-intact mice. Distinct patterns of naive cell and RTE distribution among peripheral immune organs and altered expression of CD11a were observed following IL-7 treatment in thymus-intact and thymectomized mice. These results demonstrate (1) that total TREC number and not TREC frequency accurately reflects quantitative changes in RTEs; (2) that short-term IL-7 administration results in preferential accumulations of RTEs among peripheral immune organs, accounting for the increase in TRECs in the total peripheral lymphoid pool; and (3) no evidence for regulation of thymic function by short-term IL-7 administration. (Blood. 2004;104:1110-1119)

scholarly journals Blockade of IL-7 signaling suppresses inflammatory responses and reverses alopecia areata in C3H/HeJ mice

2021 ◽  
Vol 7 (14) ◽  
pp. eabd1866
Author(s):  
Zhenpeng Dai ◽  
Eddy Hsi Chun Wang ◽  
Lynn Petukhova ◽  
Yuqian Chang ◽  
Eunice Yoojin Lee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Alopecia Areata ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Clinical Investigation ◽  
T Cell Subsets ◽  
Therapeutic Effects ◽  
Short Term ◽  
Interleukin 7

The interleukin-7 (IL-7) signaling pathway plays an important role in regulation of T cell function and survival. We detected overexpression of IL-7 in lesional skin from both humans and C3H/HeJ mice with alopecia areata (AA), a T cell–mediated autoimmune disease of the hair follicle. We found that exogenous IL-7 accelerated the onset of AA by augmenting the expansion of alopecic T cells. Conversely, blockade of IL-7 stopped the progression of AA and reversed early AA in C3H/HeJ mice. Mechanistically, we observed that IL-7Rα blockade substantially reduced the total number of most T cell subsets, but relative sparing of regulatory T cells (Tregs). We postulated that short-term anti–IL-7Rα treatment in combination with a low dose of Treg-tropic cytokines might improve therapeutic efficacy in AA. We demonstrated that short-term IL-7Rα blockade in combination with low doses of Treg-tropic cytokines enhanced therapeutic effects in the treatment of AA, and invite further clinical investigation.

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 Simplified Fluorescent Multiplex PCR Method for Evaluation of the T-Cell Receptor Vβ-Chain Repertoire

2005 ◽  
Vol 12 (4) ◽  
pp. 477-483 ◽  
Author(s):  
Sanjit Fernandes ◽  
Surendra Chavan ◽  
Vivek Chitnis ◽  
Nina Kohn ◽  
Savita Pahwa
Keyword(s):  
T Cell ◽  
Multiplex Pcr ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Clinical Samples ◽  
Cdr3 Length ◽  
Pcr Products ◽  
Pcr Method ◽  
T Cell Receptor Vβ

ABSTRACTRationale: evaluation of the T-cell receptor (TCR) Vβ-chain repertoire by PCR-based CDR3 length analysis allows fine resolution of the usage of the TCR Vβ repertoire and is a sensitive tool to monitor changes in the T-cell compartment. A multiplex PCR method employing 24 labeled upstream Vβ primers instead of the conventionally labeled downstream Cβ primer is described. Method: RNA was isolated from purified CD4 and CD8 T-cell subsets from umbilical cord blood and clinical samples using TRI reagent followed by reverse transcription using a Cβ primer and an Omniscript RT kit. The 24 Vβ primers were multiplexed based on compatibility and product sizes into seven reactions. cDNA was amplified using 24 Vβ primers (labeled with tetrachloro-6-cardoxyfluorescein, 6-carboxyfluorescein, and hexachloro-6-carboxyfluorescein), an unlabeled Cβ primer, and Taqgold polymerase. The fluorescent PCR products were resolved on an automated DNA sequencer and analyzed using the Genotyper 2.1 software. Results: Vβ spectratypes of excellent resolution were obtained with RNA amounts of 250 ng using the labeled Vβ primers. The resolution was superior to that obtained with the labeled Cβ primer assay. Also the numbers of PCRs were reduced to 7 from the 12 required in the Cβ labeling method, and the sample processing time was reduced by half. Conclusion: The method described for T-cell receptor Vβ-chain repertoire analysis eliminates tedious dilutions and results in superior resolution with small amounts of RNA. The fast throughput makes this method suitable for automation and offers the feasibility to perform TCR Vβ repertoire analyses in clinical trials.

scholarly journals Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Pavel V. Shelyakin ◽  
Ksenia R. Lupyr ◽  
Evgeny S. Egorov ◽  
Ilya A. Kofiadi ◽  
Dmitriy B. Staroverov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Subset ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Cell Compartments ◽  
Expression Of Genes ◽  
Tcr Repertoire ◽  
Antigen Presenting

The interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. Here we investigated characteristics of naïve and effector T cell subsets in XLA patients, revealing prominent alterations in the corresponding T-cell receptor (TCR) repertoires. We observed immunosenescence in terms of decreased diversity of naïve CD4+ and CD8+ TCR repertoires in XLA donors. The most substantial alterations were found within naïve CD4+ subsets, and we have investigated these in greater detail. In particular, increased clonality and convergence, along with shorter CDR3 regions, suggested narrower focused antigen-specific maturation of thymus-derived naïve Treg (CD4+CD45RA+CD27+CD25+) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve Treg proportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve Treg selection. Furthermore, the naïve Treg subset showed prominent differences at the transcriptome level, including increased expression of genes specific for antigen-presenting and myeloid cells. Altogether, our findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naïve Treg TCR repertoire that enables better control of self-reactive T cells.

INDUCTION OF SPECIFIC UNRESPONSIVENESS TO CARDIAC ALLOGRAFTS BY SHORT-TERM ADMINISTRATION OF ANTI T CELL RECEPTOR αβ ANTIBODY1

1994 ◽  
Vol 57 (2) ◽  
pp. 256-261 ◽  
Author(s):  
Masanori Tsuchida ◽  
Hiroyuki Hirahara ◽  
Yoh Matsumoto ◽  
Toru Abo ◽  
Shoji Eguchi
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Short Term ◽  
Term Administration ◽  
Cardiac Allografts

Estimating Thymic Function Through Quantification of T-Cell Receptor Excision Circles

2007 ◽  
pp. 197-214
Author(s):  
Marie-Lise Dion ◽  
Rafick-Pierre Sékaly ◽  
Rémi Cheynier
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Thymic Function ◽  
Excision Circles

scholarly journals Interleukin 7 induces CD4+ T cell-dependent tumor rejection.

1991 ◽  
Vol 174 (6) ◽  
pp. 1291-1298 ◽  
Author(s):  
H Hock ◽  
M Dorsch ◽  
T Diamantstein ◽  
T Blankenstein
Keyword(s):  
T Cell ◽  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Tumor Rejection ◽  
T Cell Subsets ◽  
Cd4 Cells ◽  
Antitumor Response ◽  
Interleukin 7

The potential of interleukin 7 (IL-7) to induce an antitumor response in vivo was analyzed. Therefore, the IL-7 gene was expressed in the plasmacytoma cell line J558L. Although the growth of IL-7-producing cells was not retarded in vitro, the IL-7-producing cells were completely rejected upon injection into mice. Tumor rejection was observed only in syngeneic but not in nude mice. The tumor-suppressive effect could be abolished by the parallel injection of an anti-IL-7 monoclonal antibody. Immunohistochemical analysis revealed IL-7-dependent infiltration of the tumor tissue by CD4+ and CD8+ T lymphocytes, and also type 3 complement receptor-positive (CR3+) cells, predominantly macrophages. Depletion of T cell subsets in tumor-bearing mice showed the absolute dependence of the antitumor response on CD4+ cells, whereas tumor rejection was unaffected by depletion of CD8+ cells. In addition to CD4+ cells, CR3+ cells were also needed for tumor rejection. The antitumor effect of IL-7 was confirmed by expression of the IL-7 gene in a second tumor cell line of different cellular origin. Together, our results demonstrate that a high local IL-7 concentration at the tumor site obtained by tumor cell-targeted gene transfer leads to tumor rejection involving a cellular mechanism that seems to be different from the ones observed in analogous experiments with other cytokines.

scholarly journals An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4-8- T cells.

1994 ◽  
Vol 180 (3) ◽  
pp. 1171-1176 ◽  
Author(s):  
P Dellabona ◽  
E Padovan ◽  
G Casorati ◽  
M Brockhaus ◽  
A Lanzavecchia
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Clone ◽  
Cell Subset ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
T Cell Clone ◽  
Gene Usage ◽  
Beta Gene

The T cell receptor (TCR)-alpha/beta CD4-8- (double negative, DN) T cell subset is characterized by an oligoclonal repertoire and a restricted V gene usage. By immunizing mice with a DN T cell clone we generated two monoclonal antibodies (mAbs) against V alpha 24 and V beta 11, which have been reported to be preferentially expressed in DN T cells. Using these antibodies, we could investigate the expression and pairing of these V alpha and V beta gene products among different T cell subsets. V alpha 24 is rarely expressed among CD4+ and especially CD8+ T cells. In these cases it is rearranged to different J alpha segments, carries N nucleotides, and pairs with different V beta. Remarkably, V alpha 24 is frequently expressed among DN T cells and is always present as an invariant rearrangement with J alpha Q, without N region diversity. This invariant V alpha 24 chain is always paired to V beta 11. This unique V alpha 24-J alpha Q/V beta 11 TCR was found in expanded DN clones from all the individuals tested. These findings suggest that the frequent occurrence of cells carrying this invariant TCR is due to peripheral expansion of rare clones after recognition of a nonpolymorphic ligand.

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