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  • 1
    Electronic Resource
    Electronic Resource
    Specificity of Two Subsets of Cytotoxic Human γδ T-Cell Clones (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 32 (1990), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peripheral blood mononuclear cells were enriched for γδ T cells by immunomagnetic separation, stimulated with cells from an allogeneic donor, and cloned. T-lymphocyte clones (TLC) of the two major γδ T-cell subsets, BB3− (i.e. Vδ2+)and δTCSI+ (i.e. Vδ1/(D)/Jδ1). were obtained. In addition, one γδ TLC was BB3−δTCSI+. All of the BB3+ TLC showed strong cytotoxicity against various allogeneic tumour cell lines, such as Daudi and K562. The cytotoxicity against the tumour cell lines was modulated by MoAb against the γδ TcR. The BB3+ TLC were not cytotoxic against B-lymphoblastoid cell lines (B-LCL). In contrast, the δTCSI+ TLC showed much lower cytotoxic activity against the tumour cell lines, but many were strongly cytotoxic against allogeneic B-LCL. Some of the δTCSI + TLC demonstrated HLA-specific cytotoxicity, while other δTCSI+ TLC had a more broad cytolytic activity against B-LCL. Thus, the two major subtypes of γδ T cells from this donor, as defined by MoAb BB3 and δTCSI, were distinct with respect to recognition specificity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1990.tb02902.x
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  • 2
    Electronic Resource
    Electronic Resource
    Interferon-γ-Secreting T Cells Localize to the Epithelium in Coeliac Disease (2002)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 56 (2002), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Increased levels of interferon-γ (IFN-γ) transcripts have previously been found in duodenal biopsy specimens from patients with untreated coeliac disease (CD). Such samples and duodenal control mucosa were therefore studied to locate and phenotype cells spontaneously secreting IFN-γ. Specimens were collected from consecutively recruited patients with untreated (seven), treated (four) or refractory (three) CD and from five histologically normal controls. Morphological and immunohistochemical examinations were performed, and epithelial and lamina propria cell suspensions were prepared from parallel samples. Unstimulated viable cells secreting IFN-γ were identified and phenotyped with a new fluorescence-activated cell sorter-based assay, and IFN-γ messenger RNA (mRNA) was analysed in snap-frozen aliquots of the same suspensions. Untreated CD cases had the highest fraction of IFN-γ+ cells in the epithelial compartment (median 2.6%, range 1.6–6.2%) and, less strikingly, in the lamina propria compartment (1.6%, range 0.3–3.6%), followed by refractory (1.4%, 1.0–1.9%; and 0.3%, 0.0–1.2%) and treated (0.8%, 0.5–0.9%; and 0.7%, 0.2–1.1%) disease and finally the controls (0.5%, 0.3–0.9%; and 0.2%, 0.1–0.7%). IFN-γ mRNA data supported these findings. IFN-γ+ intraepithelial lymphocytes were mostly CD3+ and CD8+, whereas many positive lamina propria cells were CD8–. We conclude that isolated T cells spontaneously secreting IFN-γ localize preferentially in the epithelium of patients with classical and refractory CD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2002.01195.x
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  • 3
    Electronic Resource
    Electronic Resource
    Gliadin Specific, HLA DQ2-Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls (1997)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 46 (1997), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-17.x
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  • 4
    Electronic Resource
    Electronic Resource
    Monozygotic Twins Display Differences in Their Allospecific Cytotoxic T-Cell Repertoire (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 44 (1996), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The antigen-specific repertoire of peripheral blood T lymphocytes is generated by selection in the thymus followed by peripheral immunological events. While thymic selection is predominantly under genetic control, i.e. self-HLA molecules + self-peptides, confrontation with foreign antigens will lead to expansion of given T-cells, thus modifying the T-cell repertoire. To evaluate the relative importance of such modifying events the precursor frequencies (pf) of cytotoxic T lymphocytes (CTL) against given allogeneic HLA molecules were compared in six pairs of monozygotic twins. Using limiting dilution analyses, experiments with several different allogeneic stimulator/target cell donors were performed for each twin pair. In 12 out of 17 experiments, when the twins were tested against the same stimulator/target cell donor, the CTL pf differed and the 95% confidence intervals were non-overlapping. This suggests that modifying effects by confrontation with foreign antigens play an important role in shaping the allospecific T-cell repertoire.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-357.x
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  • 5
    Electronic Resource
    Electronic Resource
    Gliadin-Specific T Cell Responses in Peripheral Blood of Healthy Individuals Involve T Cells Restricted by the Coeliac Disease Associated DQ2 Heterodimer (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 42 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Coeliac disease (CD) is probably caused by an abnormal immune response towards wheat gliadin in the small intestine. We found that gliadin-specific T cells from the small intestinal mucosa of HLA-DQ2 positive CD patients were almost exclusively restricted by the disease-associated DQ2 molecule. In the peripheral blood of CD patients, a large proportion of gliadin-specific T cells were found to be restricted by DQ molecules, including DQ2, but many were instead restricted by DR or DP molecules of the patient. We have now investigated gliadin-specific T cell responses in peripheral blood from healthy individuals. Four of 20 persons tested had strong in vitro responses and were used as donors for gliadin-specific T cell clones. We found gliadin-specific T cells restricted by the CD-associated DQ2 molecule in peripheral blood for two of these four individuals. It is the presence of such T cells also in the small intestinal mucosa which seems typical of CD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03640.x
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  • 6
    Electronic Resource
    Electronic Resource
    Gliadin Specific, HLA DQ2-Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls (1997)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 46 (1997), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1997.d01-93.x-i2
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  • 7
    Electronic Resource
    Electronic Resource
    POSITIVE SELECTION OF Tac- (CD25) POSITIVE CELLS FOLLOWING T-CELL ACTIVATION: USE OF IMMUNOMAGNETIC SEPARATION AND IMPLICATIONS FOR T-CELL CLONING (1989)
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 16 (1989), S. 0 
    Details
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We have investigated if positive selection for cells expressing activation antigens, which appear on the cell surface during T-lymphocyte activation, could be used for cloning purposes. For this purpose, we used paramagnetic, monodisperse Dynabeads coated with anti-Tac monclonal antibody, which recognizes CD25 (interleukin-2 receptor light chain). After the first 6–12 h of a primary response, depletion of Tac+ cells could largely abrogate the specific response. This indicated that the specifically responding cells were found among the Tac+ population. T-cell cloning was thus performed on Tac+ blasts positively selected after 18 h of a primary response, at day 6 of a primary response or during secondary stimulation, and gave a high percentage of specific clones. This method is thus a good alternative to established techniques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1744-313X.1989.tb00461.x
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  • 8
    Electronic Resource
    Electronic Resource
    T Cells from the Peripheral Blood of Coeliac Disease Patients Recognize Gluten Antigens when Presented by HLA-DR, -DQ, or -DP Molecules (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 39 (1994), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Coeliac disease (CD) is a T-cell mediated immunological disease of the small intestine which is precipitated in susceptible individuals by ingestion of gluten. We recently reported that gliadin-specific T cells can be found in the small intestinal mucosa of CD patients, and that a preponderance of these T cells was restricted by the CD-associated DQ(%aL*0501, βl*0201)heterodimer. Here we report studies on whether the same is found for gliadin specific T cells in the peripheral blood of CD patients. T-cell responses towards gluten antigens in vitro were found for both most CD patients and healthy controls. Gluten-specific T-cell clones (TCC) were established from four CD patients. Although a large proportion of these TCC were restricted by DQ molecules, including the CD-associated DQ(α1*0501, β1*0201) heterodimer, several were restricted instead by DR or DP molecules. Thus, gluten-derived peptides can be presented to T cells by several different HLA elass-II molecules, and the preferential DQ(#aL1*0501, β1*0201) restriction of gluten-specific T cells in the small intestinal mucosa of CD patients is less pronounced than for similar T eells in the peripheral blood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1994.tb03414.x
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  • 9
    Electronic Resource
    Electronic Resource
    Interactions between Staphylococcal Superantigens and Human T-Cell Clones are Predominantly but not Exclusively Governed by their T-Cell Receptor Vß Usage (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 39 (1994), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Stapbylococcal exotoxins (SE) are potent mitogens for human and murine T cells. Extensive studies in mice bave demonstrated strict correlations between T-cell responses to individual SE and TCR Vβ expression. Studies examining the TCR Vβ expression of SE-activated buman peripheral blood T cells also suggest close correlations, whereas the data reported using human T-cell clones (TCC) are conflicting. We bave determined tbe cDNA TCRB sequences of 52 different human TCC, expressing 35 different T-cell receptor Vfi (TCRBV)-encodcd sequences. The TCC were tested in proliferative assays using nine different SE. Most of these TCC express Vs wbicb have not been tested previously in studies examining interaction between TCC and SE. The SE stimulated a variable fractioti (1/48-31/52) ofthe TCC. Tbe ability of a given SE to stimulate TCC in many cases correlated with Vβ expression, but several exceptions were found. With one possible exception, comparisons between deduced amino-acid sequences within the ‘fourth hypervariable region’ of the TCR p chain and SE responsiveness did not reveal potential SE binding motifs. We conclude that the reactivity of T cells towards SE is governed mainly by their TCR Vβ expression. However, the authors results also suggest that the interaction between SE and human T cells may involve elements unidentified as yet which are in addition to the chain of the TCR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1994.tb03390.x
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  • 10
    Electronic Resource
    Electronic Resource
    Human T Lymphocyte Clones: Influence of Culture Conditions and Optimization of Proliferative Assays (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 30 (1989), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Many CD4+ human T lymphocyte clones (TLC) are found not to proliferate against appropriate stimulating cells, and many lose this capacity during culture. This may be due, not to a defect in the recognition of the antigen, but to an inability to produce sufficient amounts of interleukin 2 (IL-2) for autocrine growth, since specific HLA-restricted proliferative responses could be induced in ‘non-proliferative’ clones by the addition of exogenous IL-2 or phorbol myristate acetate (PMA). Of various factors tested during expansion procedures of the clones, the proliferative capacity could only be restored by changing the stimulatory cells from B lymphoblastoid cell lines (B-LCL) to peripheral blood mononuclear cells (PBM). The cytotoxicity of the TLC was found to be independent of its proliferative capacity. After restoration of the proliferative capacity, a mouse B lymphoma cell line transfected with the appropriate HLA DQA and DQB genes was still not able to induce proliferation in the absence of exogenous IL-2. We conclude that (1) ‘non-proliferative’ TLC may recognize their targets, but fail to proliferate due to temporary lack of IL-2 production, and (2) even ‘proliferative’ T cells may fail to respond to certain target cells carrying the specific antigen, such as a murine transfectant, in the absence of exogenous IL-2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1989.tb01191.x
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