A unique T-cell receptor complex expressed on human fetal lymphocytes displaying natural-killer-like activity

Abstract Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor γ chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.

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Probing Lipid Interactions of the T-cell Receptor Complex: A Micropatterning Approach

Biophysical Journal ◽

10.1016/j.bpj.2017.11.628 ◽

2018 ◽

Vol 114 (3) ◽

pp. 108a

Author(s):

Joschka Hellmeier ◽

Florian Kellner ◽

Gerhard Schuetz ◽

Johannes Huppa ◽

Eva Sevcsik

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Cell Receptor ◽

Receptor Complex ◽

Lipid Interactions

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Commitment of Common T/Natural Killer (Nk) Progenitors to Unipotent T and Nk Progenitors in the Murine Fetal Thymus Revealed by a Single Progenitor Assay

Journal of Experimental Medicine ◽

10.1084/jem.190.11.1617 ◽

1999 ◽

Vol 190 (11) ◽

pp. 1617-1626 ◽

Cited By ~ 122

Author(s):

Tomokatsu Ikawa ◽

Hiroshi Kawamoto ◽

Shinji Fujimoto ◽

Yoshimoto Katsura

Keyword(s):

T Cell ◽

Nk Cells ◽

Natural Killer ◽

T Cell Receptor ◽

Cell Lineage ◽

Cell Receptor ◽

The Other ◽

Fetal Thymus ◽

Β Chain ◽

Clonal Assay

We have established a new clonal assay system that can evenly support the development of T and natural killer (NK) cells. With this system, we show that all T cell progenitors in the earliest CD44+CD25−FcγRII/III− fetal thymus (FT) cell population retain NK potential, and that the NK lineage–committed progenitors (p-NK) also exist in this population. T cell lineage–committed progenitors (p-T), which are unable to generate NK cells, first appear at the CD44+CD25− FcγRII/III+ stage in day 12 FT. The proportion of p-T markedly increases during the transition from the CD44+CD25− stage to the CD44+CD25+ stage in day 14 FT. On the other hand, p-NK preferentially increase in number at the CD44+CD25− stage between days 12 and 14 of gestation. The production of p-NK continues up to the CD44+CD25+ stage, but ceases before the rearrangement of T cell receptor β chain genes. It was further shown that the CD44+CD25− CD122+ population of day 14 FT exclusively contains p-NK. These results indicate that the earliest T cell progenitor migrating into the FT is T/NK bipotent, and strongly suggest that the bipotent progenitor continuously produces p-NK and p-T until the CD44+CD25+ stage.

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Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3ζ, the Signaling Chain of the T-Cell Receptor Complex

Blood ◽

10.1182/blood.v91.2.585.585_585_594 ◽

1998 ◽

Vol 91 (2) ◽

pp. 585-594 ◽

Cited By ~ 2

Author(s):

Linda A. Trimble ◽

Judy Lieberman

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

T Cell ◽

T Lymphocytes ◽

T Cell Receptor ◽

Cell Receptor ◽

Receptor Complex ◽

Cd8 T Lymphocytes ◽

Immunodeficiency Virus ◽

Specific Cytotoxicity

Although human immunodeficiency virus (HIV)-infected subjects without acquired immunodeficiency syndrome have a high frequency of HIV-specific CD8 T lymphocytes, freshly isolated lymphocytes frequently lack detectable HIV-specific cytotoxicity. However, this effector function becomes readily apparent after overnight culture. To investigate reasons for T-cell dysfunction, we analyzed T-cell expression of the cytolytic protease granzyme A and of CD3ζ, the signaling component of the T-cell receptor complex. An increased proportion of CD4 and CD8 T cells from HIV-infected donors contain granzyme A, consistent with the known increased frequency of activated T cells. In 28 HIV-infected donors with mild to advanced immunodeficiency, a substantial fraction of circulating T cells downmodulated CD3ζ (fraction of T cells expressing CD3ζ, 0.74 ± 0.16 v 1.01 ± 0.07 in healthy donors; P < .0000005). CD3ζ expression is downregulated more severely in CD8 than CD4 T cells, decreases early in infection, and correlates with declining CD4 counts and disease stage. CD3ζ expression increases over 6 to 16 hours of culture in an interleukin-2–dependent manner, coincident with restoration of viral-specific cytotoxicity. Impaired T-cell receptor signaling may help explain why HIV-specific cytotoxic T lymphocytes fail to control HIV replication.

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SPECIFIC TARGET CELL LYSIS BY SUPERNATANTS DERIVED FROM ALLOIMMUNE MURINE CYTOTOXIC T LYMPHOCYTES: POSSIBLE ROLE OF A LYMPHOTOXIN-T CELL RECEPTOR COMPLEX

T and B Lymphocytes: Recognition and Function ◽

10.1016/b978-0-12-069850-9.50054-7 ◽

1979 ◽

pp. 471-479

Author(s):

John C. Hiserodt ◽

Gale A. Granger ◽

Benjamin Bonavida

Keyword(s):

T Cell ◽

T Lymphocytes ◽

T Cell Receptor ◽

Cytotoxic T Lymphocytes ◽

Target Cell ◽

Cell Lysis ◽

Cell Receptor ◽

Receptor Complex ◽

Specific Target

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Characterization of the CD3ζ, CD3γδ and CD3ε subunits of the T cell receptor complex in Atlantic salmon

Developmental & Comparative Immunology ◽

10.1016/j.dci.2007.03.015 ◽

2008 ◽

Vol 32 (1) ◽

pp. 26-35 ◽

Cited By ~ 43

Author(s):

Yun Liu ◽

Lindsey Moore ◽

Erling Olaf Koppang ◽

Ivar Hordvik

Keyword(s):

T Cell ◽

Atlantic Salmon ◽

T Cell Receptor ◽

Cell Receptor ◽

Receptor Complex

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The Transmembrane Domain of HIV-1 gp41 Inhibits T-Cell Activation by Targeting Multiple T-Cell Receptor Complex Components through Its GxxxG Motif

Biochemistry ◽

10.1021/acs.biochem.5b01307 ◽

2016 ◽

Vol 55 (7) ◽

pp. 1049-1057 ◽

Cited By ~ 12

Author(s):

Etai Rotem ◽

Eliran Moshe Reuven ◽

Yoel A. Klug ◽

Yechiel Shai

Keyword(s):

T Cell ◽

T Cell Receptor ◽

T Cell Activation ◽

Cell Activation ◽

Transmembrane Domain ◽

Cell Receptor ◽

Receptor Complex ◽

Gxxxg Motif ◽

Hiv 1 ◽

Complex Components

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Stimulation of T cells through the CD3/T-cell receptor complex: role of cytoplasmic calcium, protein kinase C translocation, and phosphorylation of pp60c-src in the activation pathway.

Molecular and Cellular Biology ◽

10.1128/mcb.7.2.650 ◽

1987 ◽

Vol 7 (2) ◽

pp. 650-656 ◽

Cited By ~ 44

Author(s):

J A Ledbetter ◽

L E Gentry ◽

C H June ◽

P S Rabinovitch ◽

A F Purchio

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Solid Phase ◽

Interleukin 2 ◽

Cell Receptor ◽

Jurkat Cells ◽

Receptor Complex ◽

Kinase C ◽

Stimulation Of

Stimulation of T cells or the Jurkat T-cell line with soluble antibodies to the CD3/T-cell receptor complex causes mobilization of cytoplasmic Ca2+, which is blocked by pertussis toxin but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and translocation of protein kinase C activity from the cytoplasm to the membrane. Such stimulation also causes phosphorylation of pp60c-src at an amino-terminal serine residue. These activities are consistent with induction of phosphatidylinositol metabolism after antibody binding. Anti-CD3 stimulation with antibody in solution, however, does not cause Jurkat cells to release interleukin 2 and blocks rather than induces proliferation of T cells. Induction of interleukin 2 production by Jurkat cells and proliferation by normal T cells requires anti-CD3 stimulation with antibody on a solid support, such as Sepharose beads or a plastic dish. Thus, we examined phosphorylation of pp60c-src after stimulation of Jurkat cells with anti-CD3 in solution or on solid phase. Both of these caused serine phosphorylation of pp60c-src that was indistinguishable even after 4 h of stimulation. These results indicate that the mode of anti-CD3 stimulation (in solution or on solid phase) controls a cellular function that modifies the consequences of signal transduction through phosphatidylinositol turnover.

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