scholarly journals gammadelta T-cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo

Immunology ◽  
2004 ◽  
Vol 111 (2) ◽  
pp. 155-164 ◽  
Author(s):  
Judith A. Kapp ◽  
Linda M. Kapp ◽  
Kyle C. McKenna ◽  
Jeffrey P. Lake
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Intraepithelial Lymphocytes ◽  
T Cell Clones ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Cell Clones ◽  
Ctl Responses

scholarly journals An Ex Vivo Study of T Lymphocytes Recovered from the Lungs of I/St Mice Infected with and Susceptible toMycobacterium tuberculosis

1998 ◽  
Vol 66 (10) ◽  
pp. 4981-4988 ◽  
Author(s):  
Irina Lyadova ◽  
Vladimir Yeremeev ◽  
Konstantin Majorov ◽  
Boris Nikonenko ◽  
Sergei Khaidukov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Antimycobacterial Activity ◽  
Enzymatic Digestion ◽  
Interleukin 4 ◽  
T Cell Clones ◽  
Cell Clones ◽  
Ifn Γ

ABSTRACT I/St mice, previously characterized as susceptible toMycobacterium tuberculosis H37Rv, were given 103 or 105 CFU intravenously. At two time points postinoculation, the cell suspensions that resulted from enzymatic digestion of lungs were enumerated and further characterized phenotypically and functionally. Regarding the T-cell populations recovered at 2 and 5 weeks postinfection, two main results were obtained: (i) the population of CD44− CD45RB+cells disappeared within 2 weeks postinfection, while the number of CD44+ CD45RB−/low cells slowly increased between weeks 2 and 5; (ii) when cocultured with irradiated syngeneic splenocytes, these lung T cells proliferated in the presence of H37Rv sonicate. Using H37Rv sonicate and irradiated syngeneic splenocytes to reactivate lung T cells, we selected five CD3+CD4+ CD8− T-cell clones. In addition to the H37Rv sonicate, the five clones react to both a short-term culture filtrate and an affinity-purified 15- to 18-kDa mycobacterial molecule as assessed by the proliferative assay. However, there was a clear difference between T-cell clones with respect to cytokine (gamma interferon [IFN-γ] and interleukin-4 [IL-4] and IL-10) profiles: besides one Th1-like (IFN-γ+ IL-4−) clone and one Th0-like (IFN-γ+ IL-4+IL-10+) clone, three clones produced predominantly IL-10, with only marginal or no IL-4 and IFN-γ responses. Inhibition of mycobacterial growth by macrophages in the presence of T cells was studied in a coculture in vitro system. It was found that the capacity to enhance antimycobacterial activity of macrophages fully correlated with INF-γ production by individual T-cell clones following genetically restricted recognition of infected macrophages. The possible functional significance of cytokine diversity among T-cell clones is discussed.

scholarly journals Early Emergence and Long-Term Persistence of HIV-Infected T Cell Clones in Children

2020 ◽  
Author(s):  
Michael J. Bale ◽  
Mary Grace Katusiime ◽  
Daria Wells ◽  
Xiaolin Wu ◽  
Jonathan Spindler ◽  
...  
Keyword(s):  
T Cell ◽  
Infected Cell ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Peripheral Blood Mononuclear ◽  
T Cell Clones ◽  
Cell Clones ◽  
Integration Sites ◽  
Infected Cells

AbstractLittle is known about the emergence and persistence of HIV-infected T cell clones in perinatally-infected children. We analyzed peripheral blood mononuclear cells for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8-17.4 months of age and with viremia suppressed for 6-9 years. We obtained 8,662 HIV-1 integration sites from pre-ART and 1,861 sites on ART. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6-9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMC infected ex-vivo showed selection for cells with proviruses integrated in BACH2 and STAT5B. Our analyses indicate that, despite marked differences in T cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.

scholarly journals The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones

2020 ◽  
Vol 26 (16) ◽  
pp. 4289-4301 ◽  
Author(s):  
Isabel C. Poschke ◽  
Jessica C. Hassel ◽  
Aaron Rodriguez-Ehrenfried ◽  
Katharina A.M. Lindner ◽  
Ignacio Heras-Murillo ◽  
...  
Keyword(s):  
T Cell ◽  
Spatial Heterogeneity ◽  
Ex Vivo ◽  
In Vitro Growth ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
T Cell Clones ◽  
Growth Capacity ◽  
Cell Clones

scholarly journals Ex Vivo Monitoring of Antigen-Specific CD4+ T Cells after Recall Immunization with Tetanus Toxoid

2007 ◽  
Vol 14 (9) ◽  
pp. 1108-1116 ◽  
Author(s):  
Catherine Barbey ◽  
Estelle Pradervand ◽  
Nathalie Barbier ◽  
François Spertini
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Tetanus Toxoid ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Effector Memory ◽  
Specific Response ◽  
T Cell Clones ◽  
Cell Clones

ABSTRACT To monitor antigen-specific CD4+ T cells during a recall immune response to tetanus toxoid (TT), a sequential analysis including ex vivo phenotyping and cytokine flow cytometry, followed by cloning and T-cell-receptor (TCR) spectratyping of cytokine-positive CD4+ T cells, was performed. Grossly, twice as many TT-specific CD4+ T-cell clones, ex vivo derived from the CCR7+/− CD69+ interleukin-2-positive (IL-2+) CD4+ subsets, belonged to the central memory (TCM; CD62L+ CD27+ CCR7+) compared to the effector memory population (TEM; CD62L− CD27− CCR7−). After the boost, a predominant expansion of the TCM population was observed with more limited variations of the TEM population. TCR beta-chain-variable region (BV) spectratyping and sequencing confirmed a large concordance between most frequently expressed BV TCR-CDR3 from ex vivo-sorted CCR7+/− CD69+ IL-2+ CD4+ subsets and BV usage of in vitro-derived TT-specific CD4+ T-cell clones, further demonstrating the highly polyclonal but stable character of the specific recall response to TT. Taken together, ex vivo flow cytometry analysis focused on the CCR7+/− CD69+ IL-2+ CD4+ subsets appears to target the bulk of antigen-specific T cells and to reach an analytical power sufficient to adequately delineate in field trials the profile of the antigen-specific response to vaccine.

Analysis of T-cell repertoires in early-stage breast carcinomas to evaluate tumor immunogenicity.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11554-11554
Author(s):  
Javier Carrasco ◽  
David Schröder ◽  
Christine Galant ◽  
Martine Berliere ◽  
Jean-Luc Re Canon ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Early Stage ◽  
Cell Receptor ◽  
Cell Infiltration ◽  
Breast Carcinomas ◽  
T Cell Clones ◽  
T Cell Infiltration ◽  
Cell Clones ◽  
Tumor Immunogenicity

11554 Background: Breast carcinomas (BC) are often considered to be weakly immunogenic and thus poorly sensitive to immunotherapy. Methods: We analyzed the repertoire of tumor-infiltrating T cells (TILs) in 41 early BC by sequencing their T cell receptor β genes (TCRβ). Libraries were built using a digital sequencing approach, barcoding each sequenced molecule to improve accuracy and quantification. T cell repertoires were also obtained from paired blood samples allowing identification of T cell clones enriched in the tumors as compared to blood. For 5 patients, CD8+ TILs were cloned ex-vivo from a tumor sample and screened for recognition of autologous predicted neoepitopes. Results: T cell infiltration differed from one tumor to another. Its amount varied of more than 30 fold and its diversity ranged from < 100 to > 5000 different clonotypes. In 34% of the tumors, there was an important T cell infiltration and we detected several clonotypes with a ≥500 fold enrichment as compared to blood. In 22% of the tumors, an important T cell infiltration was observed but without significantly enriched clonotypes. In 43% of the tumors the T cell infiltration was very limited. For 5 tumors with a high T cell infiltration, we screened ex-vivo isolated CD8+ T cell clones for recognition of predicted neoepitopes. In 4 of these tumors, with no enriched clonotypes, no recognition was observed. In 1 of these tumors, with enriched clonotypes, 6 different CD8+ T cell clones recognized 4 predicted neoepitopes. Three of these clones were > 100 fold more frequent in the tumor as compared to blood. Conclusions: About 30% of early BC were infiltrated by T cell clonotypes significantly enriched relative to blood. In one of these tumors some of the most enriched clonotypes recognized neoepitopes, demonstrating that some primary BC are spontaneously immunogenic. About 20% of the tumors had an important T cell infiltration without enriched clonotypes. None of the TIL clones isolated from 4 such tumors recognized predicted neoepitopes. Our results suggest that the detection of intratumorally enriched T cell clonotypes could identify immunogenic tumors, which may be sensitive to treatment with immunostimulatory antibodies.

scholarly journals Distribution of dominant T cell receptor beta chains in human intestinal mucosa.

1994 ◽  
Vol 180 (4) ◽  
pp. 1337-1344 ◽  
Author(s):  
G G Gross ◽  
V L Schwartz ◽  
C Stevens ◽  
E C Ebert ◽  
R S Blumberg ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Intestinal Mucosa ◽  
Polymerase Chain Reaction Amplification ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
T Cell Clones ◽  
Cell Clones ◽  
Region Length ◽  
Alpha Beta

The majority of human intestinal intraepithelial lymphocytes (iIELs) are CD8+ T cells that use the T cell receptor (TCR)-alpha/beta. Previous studies have shown that iIELs isolated from segments of small intestine or colon contain one or several dominant alpha/beta T cell clones. It is not known whether these clones expand only locally in response to a particular antigen or whether they are widely distributed throughout the intestine. To address this question, iIELs were purified from near the proximal and distal margins in a series of intestinal resections for noninflammatory diseases. TCR-beta expression was then assessed by semiquantitative polymerase chain reaction amplification, analysis of N-region length, and DNA sequencing. The previously described oligoclonal expansion of iIELs was confirmed in each sample. Identical dominant clones were identified in the proximal and distal samples from most cases, including samples taken from sites as distant as the transverse and sigmoid colon or rectum. Distinct clones were found in only one case with samples from the terminal ileum and transverse colon. These results demonstrate that a relatively small number of widely dispersed T cell clones comprise the majority of cells in the human intestinal mucosa.

Sign in / Sign up

Export Citation Format

Share Document