Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) αβ+CD8+ single-positive T cells, TCRγδ+ T cells, and natural killer–type cells in human thymus

Blood ◽  
2001 ◽  
Vol 97 (3) ◽  
pp. 601-607 ◽  
Author(s):  
Paola Romagnani ◽  
Francesco Annunziato ◽  
Elena Lazzeri ◽  
Lorenzo Cosmi ◽  
Chiara Beltrame ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Interferon Gamma ◽  
Cell Receptor ◽  
Human Thymus ◽  
Single Positive ◽  
Inducible Protein ◽  
Interferon Inducible Protein

Abstract Strong reactivity for interferon-inducible protein 10 (IP-10), monokine induced by interferon gamma (Mig), and interferon-inducible T-cell alpha chemoattractant (I-TAC) was found in epithelial cells mainly localized to the medulla of postnatal human thymus. The CXC chemokine receptor common to the 3 chemokines (CXCR3) was also preferentially expressed in medullary areas of the same thymuses and appeared to be a property of 4 distinct populations: CD3+T-cell receptor (TCR) αβ+CD8+ single-positive (SP) T cells, TCRγδ+ T cells, natural killer (NK)–type cells, and a small subset of CD3+(low)CD4+CD8+TCRαβ+double-positive (DP) T cells. IP-10, Mig, and I-TAC showed chemoattractant activity for TCRαβ+CD8+ SP T cells, TCRγδ+ T cells, and NK-type cells, suggesting their role in the migration of different subsets of mature thymocytes during human thymus lymphopoiesis.

Functional double-negative T cells in the periphery express T cell receptor Vβ gene products that cause deletion of single-positive T cells

1993 ◽  
Vol 23 (1) ◽  
pp. 250-254 ◽  
Author(s):  
Carlos Martínez-a ◽  
Miguel A. R. Marcos ◽  
Ignacio M. de Alboran ◽  
José María Alonso ◽  
Rafael de Cid ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Double Negative ◽  
Gene Products ◽  
Single Positive ◽  
Double Negative T Cells ◽  
T Cell Receptor Vβ

TiγA+δTCS1+ T cells in human thymus. Analysis of the T cell receptor

1992 ◽  
Vol 22 (7) ◽  
pp. 1947-1950 ◽  
Author(s):  
Roland Bosse ◽  
Hans Heiken ◽  
Waldemar Kolanus ◽  
Patricia Delany ◽  
Reinhold E. Schmidt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Human Thymus

scholarly journals Early Deletion and Late Positive Selection of T-Cells Expressing a Male-Specific Receptor in T-Cell Receptor Transgenic Mice

1990 ◽  
Vol 1 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Hung Sia Teh ◽  
Hiroyuki Kishi ◽  
Bernadette Scott ◽  
Peter Borgulya ◽  
Harald Von Boehmer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Early Expression ◽  
Single Positive ◽  
Selection Of

The ontogeny of T cells in T-cell receptor (TCR) transgenic mice, which express a transgenicαβheterodimer, specific for the male (H-Y) antigen in association with H-2Db, was determined. The transgenicαchain was expressed on about 10% of the fetal thymocytes on day 14 of gestation. About 50% of day-15 fetal thymocytes expressed bothαandβtranschains and virtually all fetal thymocytes expressed the transgenicαβheterodimer by day 17. The early expression of the transgenic TCR on CD4-8-thymocytes prevented the development ofγδcells, and led to accelerated growth of thymocytes and an earlier expression of CD4 and CD8 molecules. Up to day 17, no significant differences in T-cell development could be detected between female and male thymuses. By day 18 of gestation, the male transgenic thymus contained more CD4-8-thymocytes than the female transgenic thymus. The preponderance of CD4-8-thymocytes in the male transgenic thymus increased until birth and was a consequence of the deletion of the CD4+8+thymocytes and their CD4-8+precursors. By the time of birth, the male transgenic thymus contained half the number of cells as the female transgenic thymus. The deletion of autospecific precursor cells in the male transgenic mouse began only at day 18 of gestation, despite the fact that the ligand could already be detected by day 16.The preferential accumulation of CD4-8+T cells, which expressed a high density of the transgenic TCR, occurred only after birth and was .obvious in 6-week-old female thymus. These data support the hypothesis that the positive selection of T cells expressing this transgenic heterodimer may involve two steps, i.e., the commitment of CD4+8+thymocytes to the CD4-8+lineage following the interaction of the transgenic TCR with restricting major histocompatibility molecules, followed by a slow conversion of CD4+8+thymocytes into CD4-8+T cells.In normal mice, the precursors of CD+4+8 and single positive thymocytes have the CD4-8-CD3-J11d+(or M1/69+) phenotype. Because of the early expression of the transgenicαβheterodimer, this population was not detected in adult transgenic mice. All CD4-8-M1/ 69+cells expressed the transgenic receptor associated with CD3 and could be readily grown in media containing T-cell lectins and interleukin 2.

scholarly journals The Transcription Factor Interferon Regulatory Factor 1 (IRF-1) Is Important during the Maturation of Natural Killer 1.1+ T Cell Receptor–α/β+ (NK1+ T) Cells, Natural Killer Cells, and Intestinal Intraepithelial T Cells

1998 ◽  
Vol 187 (6) ◽  
pp. 967-972 ◽  
Author(s):  
Toshiaki Ohteki ◽  
Hiroki Yoshida ◽  
Toshifumi Matsuyama ◽  
Gordon S. Duncan ◽  
Tak W. Mak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Lymphocyte Subsets ◽  
Cell Receptor ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1

In contrast to conventional T cells, natural killer (NK) 1.1+ T cell receptor (TCR)-α/β+ (NK1+T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-α/α chains constitutively express the interleukin (IL)-2 receptor (R)β/15Rβ chain. Recent studies have indicated that IL-2Rβ/15Rβ chain is required for the development of these lymphocyte subsets, outlining the importance of IL-15. In this study, we investigated the development of these lymphocyte subsets in interferon regulatory factor 1–deficient (IRF-1−/−) mice. Surprisingly, all of these lymphocyte subsets were severely reduced in IRF-1−/− mice. Within CD8-α/α+ intestinal IEL subset, TCR-γ/δ+ cells and TCR-α/β+ cells were equally affected by IRF gene disruption. In contrast to intestinal TCR-γ/δ+ cells, thymic TCR-γ/δ+ cells developed normally in IRF-1−/− mice. Northern blot analysis further revealed that the induction of IL-15 messenger RNA was impaired in IRF-1−/− bone marrow cells, and the recovery of these lymphocyte subsets was observed when IRF-1−/− cells were cultured with IL-15 in vitro. These data indicate that IRF-1 regulates IL-15 gene expression, which may control the development of NK1+T cells, NK cells, and CD8-α/α+ IELs.

scholarly journals T-Cell Receptor Gene Therapy for Human Papillomavirus–Associated Epithelial Cancers: A First-in-Human, Phase I/II Study

2019 ◽  
Vol 37 (30) ◽  
pp. 2759-2768 ◽  
Author(s):  
Stacey L. Doran ◽  
Sanja Stevanović ◽  
Sabina Adhikary ◽  
Jared J. Gartner ◽  
Li Jia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phase I ◽  
Antigen Presentation ◽  
T Cell Receptor ◽  
Interferon Gamma ◽  
Cell Receptor ◽  
Genetically Engineered ◽  
T Cell Therapy ◽  
Epithelial Cancers

PURPOSE Genetically engineered T-cell therapy is an emerging treatment of hematologic cancers with potential utility in epithelial cancers. We investigated T-cell therapy for the treatment of metastatic human papillomavirus (HPV)–associated epithelial cancers. METHODS This phase I/II, single-center trial enrolled patients with metastatic HPV16-positive cancer from any primary tumor site who had received prior platinum-based therapy. Treatment consisted of autologous genetically engineered T cells expressing a T-cell receptor directed against HPV16 E6 (E6 T-cell receptor T cells), a conditioning regimen, and systemic aldesleukin. RESULTS Twelve patients were treated in the study. No dose-limiting toxicities were observed in the phase I portion. Two patients, both in the highest-dose cohort, experienced objective tumor responses. A patient with three lung metastases experienced complete regression of one tumor and partial regression of two tumors, which were subsequently resected; she has no evidence of disease 3 years after treatment. All patients demonstrated high levels of peripheral blood engraftment with E6 T-cell receptor T cells 1 month after treatment (median, 30%; range, 4% to 53%). One patient’s resistant tumor demonstrated a frameshift deletion in interferon gamma receptor 1, which mediates response to interferon gamma, an essential molecule for T-cell–mediated antitumor activity. Another patient’s resistant tumor demonstrated loss of HLA-A*02:01, the antigen presentation molecule required for this therapy. A tumor from a patient who responded to treatment did not demonstrate genetic defects in interferon gamma response or antigen presentation. CONCLUSION Engineered T cells can induce regression of epithelial cancer. Tumor resistance was observed in the context of T-cell programmed death-1 expression and defects in interferon gamma and antigen presentation pathway components. These findings have important implications for development of cellular therapy in epithelial cancers.

scholarly journals Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153347 ◽  
Author(s):  
Nyambayar Dashtsoodol ◽  
Tomokuni Shigeura ◽  
Ritsuko Ozawa ◽  
Michishige Harada ◽  
Satoshi Kojo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Natural Killer T Cells ◽  
Α Chain ◽  
Killer T Cells ◽  
Deficient Mice ◽  
Natural Killer T

scholarly journals The Single Positive T Cells Found in CD3-ζ/η−/− Mice Overtly React with Self–Major Histocompatibility Complex Molecules upon Restoration of Normal Surface Density of T Cell Receptor–CD3 Complex

1997 ◽  
Vol 185 (4) ◽  
pp. 707-716 ◽  
Author(s):  
Shih-Yao Lin ◽  
Laurence Ardouin ◽  
Anne Gillet ◽  
Marie Malissen ◽  
Bernard Malissen
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Normal Density ◽  
Cell Receptors ◽  
Peripheral T Cells ◽  
Single Positive ◽  
Deficient Mice

CD3-ζ/η–deficient mice have small thymuses containing cells that show a profound reduction in the surface levels of T cell receptors and terminate their differentiation at the CD4+CD8+ stage. Rather unexpectedly, CD3− or very low single positive T cells accumulate over time in the spleen and lymph nodes of CD3-ζ/η–deficient mice after a process dependent on MHC expression. Fusion of these peripheral T cells with a CD3-ζ–positive derivative of the BW5147 TCR-α−/β− thymoma resulted in hybridomas that do express an heterogeneous set of T cell receptor α/β dimers at their surface and at density comparable to those found in hybridomas derived from wild-type peripheral T cells. We have investigated the specificities of these T cell receptors using spleen cells from congenic and mutant mouse strains, and showed that the majority of them readily recognized self-MHC class I or class II molecules. These results demonstrate that by increasing the density and/or output of the T cell receptors expressed in peripheral T cells, one can confer them with the capacity to respond to normal density of self-MHC molecules.

scholarly journals Signal transduction by the CD2 antigen in T cells and natural killer cells: requirement for expression of a functional T cell receptor or binding of antibody Fc to the Fc receptor, Fc gamma RIIIA (CD16).

1991 ◽  
Vol 174 (6) ◽  
pp. 1407-1415 ◽  
Author(s):  
L L Spruyt ◽  
M J Glennie ◽  
A D Beyers ◽  
A F Williams
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Cell Receptor ◽  
Fc Receptor ◽  
Jurkat Cells

Crosslinking of CD2 antigen on T lymphocytes and natural killer (NK) cells leads to a rise in cytoplasmic-free Ca2+ concentration ([Ca2+]i). However, CD2 seems unlikely to interact directly with the second messenger pathways since signaling via CD2 is poor in T cells that lack the T cell receptor (TCR) and is absent in L cells or insect cells that express CD2. In contrast, NK cells that are also TCR- can be triggered via CD2, but it is unclear as to whether the CD16 Fc receptor (FcR) may facilitate this effect. The CD16 transmembrane molecule is expressed in a complex with the zeta homodimer or the zeta/gamma heterodimer and these dimers are also associated with the TCR complex. Thus, it seemed that zeta chains may provide the link between signaling on NK cells and T cells. This could be tested on TCR- cells since when CD16 is transfected into T cells it is expressed in a complex with TCR zeta homodimer or the zeta/gamma heterodimer. At first, potentiation of CD2 signaling was seen on TCR- Jurkat cells expressing CD16, but this was found to be dependent on trace levels (1%) of IgG in F(ab')2 antibody preparations. With pure F(ab')2, the effect was lost. Signaling on a rat NK cell line was also re-examined with F(ab')2 antibodies that had no IgG contamination, and again no signal transduction via CD2 was seen. We thus conclude that there is no clear evidence for potent signaling via CD2 on cells that lack a TCR complex and that TCR zeta chain expressed at the cell surface is not sufficient to potentiate signaling via CD2 as measured by an increase in [Ca2+]i.

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