Cell surface cathepsin G can be used as an additional marker to distinguish T cell subsets

Abstract Using monoclonal antibodies to cell surface antigens and fluorescent cell sorter analysis, we studied peripheral blood lymphocyte subsets after bone marrow transplantation (BMT). In 13 patients studied 3 mo or more after BMT, the ratio of T-cell subsets defined by antibodies OKT4 and OKT8 was reversed (OKT4/OK%8 = 0.7 +/- 0.3) in comparison to normal volunteers or bone marrow donors (ratio OKT4/OKT8 = 1.7 +/- 0.4) (p less than 0.001). This reversed ratio persisted for up to 3 yr after BMT. In contrast to a previous report, presence of an abnormal ratio of T-cell subsets did not correlate with clinically significant graft- versus-host disease (GVHD). In agreement with a previous study, (26% +/- 8%; less than 4% in normals (p less than 0.001) and antibody OKT10 reactive cells (39% +/- 20% versus 10% +/- 4%) (p less than 0.01), suggesting in vivo activation. However, their PBL did not react with antibody B3/25 (antitransferrin receptor), a marker found on normal PBL after in vitro activation by mitogens (BMT patients less than 5%; normal PBL T cells plus PHA 45% +/- 11%). These results demonstrate that BMT patients have: (A) an abnormal ratio of T-cell subsets in the presence or absence of clinically significant GVDH disease so that these measurements were not useful in monitoring patients; (B) an increased number of T cells with cell surface phenotype (OKT8+, Ia+, OKT10+, B3/25-) that is distinct from normals but similar to patients with infectious mononucleosis or acquired hypogammaglobulinemia.

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T suppressor cell growth factor and anti-CD3 antibodies stimulate reciprocal subsets of T lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.166.2.404 ◽

1987 ◽

Vol 166 (2) ◽

pp. 404-418 ◽

Cited By ~ 18

Author(s):

E J Fox ◽

D E Lewis ◽

K P Deemer ◽

M N ElMasry ◽

R R Rich

Keyword(s):

T Cell ◽

Growth Factor ◽

Cell Growth ◽

Cell Surface ◽

Suppressor Cell ◽

Cell Receptor ◽

T Cell Subsets ◽

Dependent Manner ◽

Cell Surface Antigens ◽

Cd8 Cells

Because of the central role of IL-2 in clonal expansion of T cells, we have postulated that lymphocyte subpopulations with opposing regulatory functions might be independently regulated by differential requirements for expression of cell-surface IL-2-R. Purified CD4+ and CD8+ cells proliferated in an IL-2-dependent manner to crosslinked anti-T cell receptor antibodies (anti-CD3-Seph). Similarly, both CD4+ and CD8+ cells became IL-2 responsive after incubation in T suppressor cell growth factor (TsGF), a newly described approximately 8,000 Mr product of activated CD4+ cells. In support of our hypothesis, however, we observed that subpopulations of CD4+ and CD8+ cells, possessing distinct cell-surface antigens, showed differential responses to these stimuli. Those cells of suppressor-inducer or suppressor-effector phenotype failed to proliferate when cultured in anti-CD3-Seph plus IL-2, but did proliferate in an IL-2-dependent manner to TsGF. Furthermore, the suppressor-effector population was unresponsive to TsGF plus IL-2 when cocultured in anti-CD3-Seph, suggesting that functionally induced Ts may be refractory to growth stimuli. Conversely, cells with helper-inducer or cytolytic phenotype proliferated when incubated in anti-CD3-Seph and IL-2, while remaining essentially unresponsive to TsGF and IL-2. The results could not be explained by differences in the level of CD3 expression by the T cell subsets. Thus, cells within the helper and suppressor lineages appear to have distinct and reciprocal patterns for the induction of IL-2 responsiveness.

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Re-investigation of classic T cell subsets and identification of novel cell subpopulations by single-cell RNA sequencing

10.1101/2021.02.11.430754 ◽

2021 ◽

Author(s):

Xuefei Wang ◽

Xiangru Shen ◽

Shan Chen ◽

Hongyi Liu ◽

Ni Hong ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Surface ◽

Single Cell ◽

Rna Sequencing ◽

T Cell Activation ◽

Expression Profiles ◽

T Cell Subsets ◽

Cell Subpopulation ◽

Single Cell Rna Sequencing

AbstractClassic T cell subsets are defined by a small set of cell surface markers, while single cell RNA sequencing (scRNA-seq) clusters cells using genome-wide gene expression profiles. The relationship between scRNA-seq Clustered-Populations (scCPops) and cell surface marker-defined classic T cell subsets remain unclear. Here, we interrogated 6 bead-enriched T cell subsets with 62,235 single cell transcriptomes and re-grouped them into 9 scCPops. Bead-enriched CD4 Naïve and CD8 Naïve were mainly clustered into their scCPop counterparts, while cells from the other T cell subsets were assigned to multiple scCPops including mucosal-associated invariant T cells and natural killer T cells. The multiple T cell subsets that form a single scCPop exhibited similar expression pattern, but not vice versa, indicating scCPops are much homogeneous cell populations with similar cell states. Interestingly, we discovered and named IFNhi T, a new T cell subpopulation that highly expressed Interferon Signaling Associated Genes (ISAGs). We further enriched IFNhi T by FACS sorting of BST2 for scRNA-seq analyses. IFNhi T cluster disappeared on tSNE plot after removing ISAGs, while IFNhi T cluster showed up by tSNE analyses of ISAGs alone, indicating ISAGs are the major contributor of IFNhi T cluster. BST2+ T cells and BST2− T cells showing different efficiencies of T cell activation indicates high level of ISAGs may contribute to quick immune responses.

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Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins

Virology ◽

10.1016/j.virol.2017.12.036 ◽

2018 ◽

Vol 516 ◽

pp. 21-29 ◽

Cited By ~ 3

Author(s):

Mingce Zhang ◽

Tanya O. Robinson ◽

Alexandra Duverger ◽

Olaf Kutsch ◽

Sonya L. Heath ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Surface ◽

Cd4 T Cells ◽

Regulatory Proteins ◽

T Cell Subsets ◽

Cd4 T Cell ◽

Hiv 1

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Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis

Clinical Immunology ◽

10.1006/clim.2001.5003 ◽

2001 ◽

Vol 99 (2) ◽

pp. 253-265 ◽

Cited By ~ 26

Author(s):

Laura-Inés Salazar-Fontana ◽

Eva Sanz ◽

Isabel Mérida ◽

Antonio Zea ◽

Ana Sanchez-Atrio ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Cell Surface ◽

T Cell Subsets ◽

Cd4 T Cell ◽

Abnormal Expression

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Expression and Function of Tigit in B-Cell Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v128.22.4138.4138 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4138-4138 ◽

Cited By ~ 2

Author(s):

Zhi-Zhang Yang

Keyword(s):

T Cells ◽

T Cell ◽

Cell Surface ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cd8 T Cells ◽

Immune Checkpoint ◽

T Cell Subsets ◽

Non Hodgkin Lymphoma ◽

And Function

Background:T cell Ig and ITIM domain (TIGIT) is an immune checkpoint molecule and a novel member of CD28 family. TIGIT is expressed on NK cells, effector and memory T cells, and Treg cells. Upon ligation with CD155, TIGIT delivers an inhibitory signal and negatively regulates anti-tumor responses. While important in normal T-cell biology, the expression and function of TIGIT in the blood and tumor microenvironment of patients with B-cell non-Hodgkin lymphoma (NHL) is completely unknown. Goal: To phenotypically and functionally characterize TIGIT+T cell subsets in B-cell NHL and compare expression of TIGIT on intratumoral T cells to normal controls. Results: In peripheral blood, TIGIT expression was not detected on resting T cells. In contrast, when we analyzed biopsy specimens from B-cell NHL patients, we observed that TIGIT is variably but highly expressed on a subset of intratumoral T cells. A median of 41.1% (range: 24.9-56.1, n=5) of CD4+ or 22.2% (range: 13.4-33.3, n=5) of CD8+ T cells from tumor specimens expressed TIGIT on the cell surface. In normal tonsil tissue, expression level of TIGIT was modest or negligible. A median of 12.0% (range: 9.1-15.8, n=5) of CD4+ or 3.9% (range: 1.3-5.7, n=5) of CD8+ T cells express TIGIT on the cell surface, which is significantly lower than that in B-cell NHL (p=0.005 and p=0.003 for CD4+ and CD8+, respectively). We observed that both CD45RA+ and CD45RA- T cells express TIGIT with the greatest expression on the CD45RA- population in B-cell NHL specimens. Furthermore, we found that TIGIT+ T cells coexpressed other immune checkpoint molecules including PD-1 and TIM-3. Functionally, TIGIT+ T cells displayed reduced cytokine production, as the number of IFN-γ- and IL-2-producing cells was lower in the TIGIT+ population than in TIGIT-T cells. Unlike TIM-3 that is coexpressed with PD-1 and whose expression is upregulated by IL-12, TIGIT expression is not upregulated by IL-12, suggesting that a different mechanism is involved in TIGIT upregulation in B-cell NHL. Conclusion: Taken together, these results indicated that TIGIT is highly expressed on intratumoral T cells in B-cell NHL and is expressed on a population of T-cells with suppressed immune function. TIGIT, while co-expressed with PD-1 and TIM-3, is not upregulated by cytokines such as IL-12, suggesting that it is regulated by an alternate pathway. Inhibition of TIGIT signaling may be an additional mechanism to prevent T-cell suppression and exhaustion in B-cell NHL. Disclosures No relevant conflicts of interest to declare.

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Functional and biochemical characterization of a secreted I-J(+) suppressor factor that binds to immunoglobulin.

Journal of Experimental Medicine ◽

10.1084/jem.163.6.1415 ◽

1986 ◽

Vol 163 (6) ◽

pp. 1415-1432 ◽

Cited By ~ 8

Author(s):

M J Daley ◽

M Nakamura ◽

M L Gefter

Keyword(s):

T Cell ◽

Cell Surface ◽

T Cell Receptor ◽

Biochemical Characterization ◽

Cell Receptor ◽

T Cell Subsets ◽

Cytotoxic T Cell ◽

Suppressor Activity ◽

Suppressor Factor ◽

T Cell Receptor Genes

A secreted product of a T cell leukemic cell line, LH-8, was examined for its biochemical and biological properties. The factor that we have termed Immunoglobulin-Binding T cell Suppressor Factor (IgB-TsF) was shown to be suppressive for the in vitro and in vivo humoral response to a variety (but not all) antigens tested. The cell surface phenotype of the LH-8.1 subclone was M.Ig(-), Thy-1(+), L3T4(-), Lyt-2(+), FcR(-), MAC-1(-), and H-2b(+). In addition, both the cell surface and secreted factor, IgB-TsF, of LH-8.1 expressed determinants that were recognized by anti-I-Jb mAbs but not by an anti-I-Jd monoclonal. The same factor also retained an affinity for the Fc portion of approximately 30% of randomly selected, purified mAbs. This binding could be abolished if the Fab or F(ab')2 fragments of these mAb were used, but was found to be unrelated to isotype of the respective mAbs. Using subclones that expressed quantitative differences in their ability to exert suppression as sources of biosynthetically labeled IgB-TsF, we have shown the suppressor activity correlated with a single, 28 kD protein. Furthermore, comparisons of these same subclones that differ in their suppressor activity, do not show any direct correlation of this biological activity with the expression of the previously described T cell receptor genes. It also suggests that at least some suppressor cell subsets may use the same or related family of T cell receptor genes for their recognitive stage of activation as helper and cytotoxic T cell subsets, but not for their effector stage of immunologic suppression.

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T-cell subsets in multiple sclerosis: A comparative study between cell surface antigens and function

Clinical Immunology and Immunopathology ◽

10.1016/0090-1229(84)90120-x ◽

1984 ◽

Vol 32 (2) ◽

pp. 185-197 ◽

Cited By ~ 19

Author(s):

Ulla Tjernlund ◽

Pierre Cesaro ◽

Elizabeth Tournier ◽

Jean-Denis Degos ◽

Jean-François Bach ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Cell Surface ◽

Comparative Study ◽

Surface Antigens ◽

T Cell Subsets ◽

Cell Surface Antigens ◽

And Function

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Distinctive CD26 Expression on CD4 T-Cell Subsets

Biomolecules ◽

10.3390/biom11101446 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1446

Author(s):

Oscar J. Cordero ◽

Carlos Rafael-Vidal ◽

Rubén Varela-Calviño ◽

Cristina Calviño-Sampedro ◽

Beatriz Malvar-Fernández ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Surface ◽

Cd4 T Cells ◽

Ex Vivo ◽

T Cell Subsets ◽

Effector Memory ◽

T Helper ◽

Cd26 Expression

Immune system CD4 T-cells with high cell-surface CD26 expression show anti-tumoral properties. When engineered with a chimeric antigen receptor (CAR), they incite strong responses against solid cancers. This subset was originally associated to human CD4 T helper cells bearing the CD45R0 effector/memory phenotype and later to Th17 cells. CD26 is also found in soluble form (sCD26) in several biological fluids, and its serum levels correlate with specific T cell subsets. However, the relationship between glycoprotein sCD26 and its dipeptidyl peptidase 4 (DPP4) enzymatic activity, and cell-surface CD26 expression is not well understood. We have studied ex vivo cell-surface CD26 and in vitro surface and intracellular CD26 expression and secretome’s sCD26 in cultured CD4 T cells under different polarization conditions. We show that most human CD26negative CD4 T cells in circulating lymphocytes are central memory (TCM) cells while CD26high expression is present in effector Th1, Th2, Th17, and TEM (effector memory) cells. However, there are significant percentages of Th1, Th2, Th17, and Th22 CD26 negative cells. This information may help to refine the research on CAR-Ts. The cell surface CD45R0 and CD26 levels in the different T helper subsets after in vitro polarization resemble those found ex vivo. In the secretomes of these cultures there was a significant amount of sCD26. However, in all polarizations, including Th1, the levels of sCD26 were lower (although not significantly) compared to the Th0 condition (activation without polarization). These differences could have an impact on the various physiological functions proposed for sCD26/DPP4.

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