The HLA Likes and Dislikes of Allospecific and Non‐MHC‐Restricted Cytotoxic T Lymphocytes

Nößner, E.; Falk, Christine S.; Jantzer, Petra; Reinhardt, Cahsten; Steinle, Alexander; Schendel, Dolores J.

doi:10.1111/j.1600-065x.1996.tb00931.x

Cited by 7 publications

(4 citation statements)

References 136 publications

(89 reference statements)

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“…Epithelial tumor cells (RCC26) were lysed by NK-like T cells of all donors but sometimes only to a low extent. In concordance with previous studies, the non-specific cytotoxicity of NK-like T cells affects tumor cells of hematological as well as non-hematopoietic origins and the individual HLA class I levels represent important parameters for the regulation of NK and NKlike T cells [32,33].…”

Section: Discussionsupporting

confidence: 88%

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TCR‐independent cytokine stimulation induces non‐MHC‐restricted T cell activity and is negatively regulated by HLA class I

et al. 2006

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Recent evidence suggests that the functional status of T cells activated independently from their TCR differs substantially from classical MHC-restricted T cells. Here, we show that TCR-independent, short-term stimulation via the common c-chain of the IL-2/IL-15 receptor induces non-MHC-restricted cytotoxicity and sustained cytokine secretion in purified CD4 + or CD8 + T cells. NK-like cytotoxicity is directed against MHC class Inegative targets and can be inhibited by classical and non-classical HLA class I molecules. Known inhibitory receptors, such as CD85j (ILT2) and leukocyte-associated Ig-like receptor-1, are not responsible for this HLA-mediated inhibition. NK-like cytotoxicity can be costimulated by NKG2D (CD314) triggering, but 2B4 (CD244) and DNAM-1 (CD226) are not involved. NK-like T cells display an activated phenotype and secrete various cytokines, including IFN-c, TNF-a, IL-5, IL-13 and MIP-1b. Under normal conditions, HLA class I-mediated inhibition may function as a safety mechanism to prevent unbalanced cytokine production and effector killing mechanisms by T cells that were activated independently from their TCR. Non-MHC-restricted activity represents a functional status rather than a property of distinct T cell subpopulations. Thus, cytokine-induced, non-MHC-restricted T cells may be relevant in immune responses against tumors showing aberrant MHC expression through their capacities of cytokine production and direct tumor cell eradication.

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Section: Discussionsupporting

confidence: 88%

“…Cells were fixed with PBS/1% PFA, washed and permeabilized with 0.35% saponin. After addition of perforin-FITC (dG9) or IgG2b-FITC (27)(28)(29)(30)(31)(32)(33)(34)(35), isotype control; Becton Dickinson), T cells were washed twice with 0.1% saponin and analyzed by flow cytometry.…”

Section: Intracellular Perforin Stainingmentioning

confidence: 99%

TCR‐independent cytokine stimulation induces non‐MHC‐restricted T cell activity and is negatively regulated by HLA class I

et al. 2006

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“…The HLA-C molecule is recognized by Killer Immunoglobulin-like Receptors (KIR)s, KIR2DL1 and KIR2DL2,3. Amongst the CD4 + T cells there is a subgroup of cells characterized by non-MHC restricted cytotoxicity, with Natural Killer (NK)-like activity and HLA-Cw7 dependent inhibition of cytotoxic activity [21][22][23][24]. Methylation in HLA-C may therefore affect cytotoxic activity mediated by CD4 + T cells and may suggest a role of HLA-C restricted T cell response in CFS/ME.…”

Section: Discussionmentioning

confidence: 99%

Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Brenu

Staines²,

Marshall‐Gradisnik³

2014

J Clin Cell Immunol

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Objective: Methylation is known to regulate biological processes and alterations in methylation patterns have been associated with a variety of diseases. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an unexplained disorder associated with immunological and molecular changes. CD4 + T cells specifically, regulatory T cells (Tregs) have been implicated in CFS/ME patients where significant increases in Tregs have been observed in these patients. Therefore the objective of this study was to examine methylation in CD4 + T cells from CFS/ME patients. Methods: The study comprised twenty-five CFS/ME participants and eighteen controls aged between 25-60 years. A volume of 20 ml whole blood was collected from each participant and peripheral blood mononuclear cells were isolated via density gradient centrifugation. A negative isolation kit was used to isolate the CD4 + T cells from the peripheral blood samples. Genome wide methylation studies were performed on isolated CD4 + T cells using the Illumina Infinium 450 K Human methylation array system. Data analysis was performed using Genome studio and Partek Enrichment software. Results: 120 CpGs were observed to be differentially methylated in the CFS/ME patients in comparison to the controls. Of these 70 were associated with known genes. The majority of the differential methylated regions in the CFS/ME patients were hypomethylated. Additionally, most of the genes with differentially methylated regions in the CFS/ME patients were responsible for apoptosis, cell development, cell function and metabolic activity. Conclusion: The present study demonstrates that epigenetic changes in CD4 + T cells may have a potential role in the immunological changes observed in CFS/ME patients.

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“…Indeed, the present study showed a strong lysis of K562 cells in some patients, providing evidence for the contribution of MHC‐unrestricted cytotoxicity. Immunophenotyping confirmed the existence of CD3+/CD56+ cells after autologous PBSCT, and these cells may have acted as non‐MHC‐restricted effector cells in our experiments, as has been shown for a subset of CD3+ lymphocytes with NK cell‐like properties ( Falk et al ., 1995 ; Nossner et al ., 1996 ; Mingari et al ., 1998 ). As it is known that certain viruses or tumours may escape from the specific CTL response in vivo , these unspecific effector mechanisms may play a very important role in host defence against viral pathogens or tumour cells ( Maudsley & Pound, 1991; Schendel et al ., 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of the cellular immune response after autologous peripheral blood stem cell transplantation in patients with non‐Hodgkin's lymphoma

Nolte

Buhmann

Emmerich³

et al. 2000

Br J Haematol

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Peripheral blood stem cell (PBSC) transplants may be depleted of lymphoid progenitors, thereby disabling the cellular immune response against viral pathogens after autologous PBSC transplantation (PBSCT). To monitor the cellular immune reconstitution after autologous PBSCT, we investigated the cytolytic activity (CLA) of peripheral blood T lymphocytes against Epstein-Barr virus (EBV) in 13 patients with non-Hodgkin's lymphoma or multiple myeloma. The individual EBV-directed CLA (EBV-CLA) was determined by calculating the number of cytolytic effector cells in 106 T cells needed to lyse 25% of autologous EBV-transformed B-lymphoblastoid cells, expressed as lytic units (LU25). During the first 6 months after PBSCT, the EBV-CLA was only 14.6% of the response of healthy controls (median 4. 8 vs. 32.9 LU25). Thereafter, the EBV-CLA increased to 28.15 LU25 (median) or 86% of healthy controls. Monthly follow-up analyses in five selected patients showed that the EBV-CLA was barely detectable at 4 weeks and recovered at 8-12 weeks after PBSCT in four out of five patients. Effector cells consisted mostly of CD8-positive T lymphocytes, with small CD4- and CD3/CD56-positive lymphocyte fractions. These results suggest that the reconstitution of the cellular immune response against EBV takes 8-12 weeks after autologous PBSCT.

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The HLA Likes and Dislikes of Allospecific and Non‐MHC‐Restricted Cytotoxic T Lymphocytes

Cited by 7 publications

References 136 publications

TCR‐independent cytokine stimulation induces non‐MHC‐restricted T cell activity and is negatively regulated by HLA class I

TCR‐independent cytokine stimulation induces non‐MHC‐restricted T cell activity and is negatively regulated by HLA class I

Methylation Profile of CD4+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Reconstitution of the cellular immune response after autologous peripheral blood stem cell transplantation in patients with non‐Hodgkin's lymphoma

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