Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains [see comments]

Totero, Daniela de; Tazzari, Pl; DiSanto, JP; Celle, PF di; Raspadori, Donatella; Conte, Romana; Gobbi, Marco; Ferrara, G.B.; Flomenberg, Neal; Lauria, F.

doi:10.1182/blood.v80.7.1765.1765

Cited by 30 publications

(8 citation statements)

References 32 publications

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“…Immunofluorescence analysis of cell surface antigen expression. Flow cytometric analyses of total CLL mononuclear cells and of T-cell-enriched fractions were performed by one-, two-or three-colour immunofluorescence, as previously described (de Totero et al, 1992). Briefly, direct immunofluorescence labelling was carried out with anti-CD2, -CD19, -CD3, -TCRa/b, -CD4, -CD8, -CD57, -CD16, -DR (all from Becton Dickinson), -CD30 (Dakopatts, Glostrup, Denmark) and anti-CD14 (Ortho) moAbs labelled with fluorescein (FITC) or with anti-CD28 moAb labelled with phycoerythrin (PE) (Becton Dickinson), and 1 × 10 5 cells/sample were incubated with the labelled antibody for 30 min on ice.…”

Section: Methodsmentioning

confidence: 99%

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IL4 production and increased CD30 expression by a unique CD8⁺ T‐cell subset in B‐cell chronic lymphocytic leukaemia

et al. 1999

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Summary. Phenotypic and functional abnormalities within the residual non-B-cell compartment of B-cell chronic lymphocytic leukaemia (CLL) suggest an interaction between tumour cells and host immune effectors. To explore the possibility of a polarized Th1/Th2 response we have studied CD30 antigen expression and the pattern of cytokine production by purified CLL T cells. Activated T cells from CLL patients showed a significant increase in the expression of CD30 compared to normal controls. Accordingly, high levels of soluble CD30 were detected in supernatants from activated T-cell cultures, as well as in CLL serum samples. Messenger RNA for IL4 was found in both resting and, to a greater extent, in activated CLL T lymphocytes. The latter cells were also capable of releasing IL4. Three-colour immunofluorescence analyses revealed a strong CD30 expression in the CD3þ /CD28 ¹ large granular lymphocyte subset, which is considerably expanded in CLL. Production of IL4, as well as expression and release of CD30 by these T cells, was conclusively demonstrated at the clonal level. These findings document an expansion of a peculiar subset of 'Th2-like' cells in CLL, with an increased IL4 production and CD30 expression and release, that are likely to contribute to both the B-cell accumulation and immunedefects characteristic of this disease.

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Section: Methodsmentioning

confidence: 99%

“…The mean percentage of CD8 þ / CD28 ¹ /CD30 þ cells was 33 Ϯ 9·8%. Since LGL-like T cells do not express the CD28 antigen (de Totero et al, 1992), it is conceivable that a large fraction of the CD30 þ cells detected following PHA activation was representative of this subset.…”

Section: Cd28 Expression On Cd30 þ T Cellsmentioning

confidence: 99%

IL4 production and increased CD30 expression by a unique CD8⁺ T‐cell subset in B‐cell chronic lymphocytic leukaemia

et al. 1999

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“…Unlike normal thymic DP cells and the majority of CD8 SP T cells, both of which express heterodimeric a/b subunits, a subpopulation of NK cells and T lymphocytes expresses a CD8 aa homodimer. Isoform analysis of the three present CD4/CD8 DP patients, who had low CD8 expression, revealed that their CD8 was composed of a CD8aa homodimer, as in some DP T-LGL patients previously reported (de Totero et al, 1992;Mizuki et al, 1998). CD4 SP cells can reacquire CD8 and become CD4 + CD8 dim T cells, in response to physiological stimuli, because the CD8 genes in CD4 cells are unmethylated.…”

Section: Discussionmentioning

confidence: 60%

TCR Vβ repertoire analysis in CD56⁺ CD16^dim/− T‐cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes

Karasawa

Mitsui²,

Isoda³

et al. 2003

Br J Haematol

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Summary.We report 10 patients with T-cell large granular lymphocyte (LGL) leukaemia: four patients had CD16 + CD56 ) LGL lymphocytes (typical for LGL leukaemia), and six patients had CD56 + CD16 dim/) LGL lymphocytes (atypical). Among the CD56 + CD16 dim/) patients, LGL lymphocytes were CD4 + CD8 ) in one patient, CD4/CD8 double positive (DP) in three, and CD4 ) CD8 + in two. The CD4 + CD8 dim DP cells expressed a CD8aa homodimer. T-cell receptor (TCR) Vb complementarity-determining region 3 (CDR3) size distribution analysis and direct sequencing identified at least 1 in-frame clonal TCR Vb transcript in each patient; three patients had two or three different clonal sequences. To determine whether these transcripts were translated into cell surface TCR, we performed flow cytometric analysis using Vb monoclonal antibodies (mAbs). A single Vb protein was identified in patients, even those with multiple in-frame transcripts. Previous and present results suggest that CD56 + CD16 dim/) LGL leukaemia is more common than previously thought, and is associated with unusual phenotypes. When assessed using only molecular techniques, the monoclonal status of this disease may be misinterpreted as oligoclonal; thus, flow cytometric analysis using Vb mAb is quite useful. Because mAbs do not cover the entire Vb repertoire, assessing clonality using a combination of molecular methods and mAbs is preferable.

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“…Moreover, most CD8^ cells among intermediate TCR cells in mice have the aa homodimer of CD8 antigens [5]. Similarly, it has been reported that CD57 ' T cells in humans also have the an homodimer of CD8 antigens [37]. Namely.…”

Section: Discussionmentioning

confidence: 99%

Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer

Okada

Iiai

Kawachi

et al. 1995

Clinical and Experimental Immunology

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SUMMARY Human T cells carrying natural killer (NK) markers, CD57 or CD56 antigens, appear to be distinguishable from other T cell subsets in terms of their granular lymphocyte morphology and their numerical increase in patients with AIDS and in recipients of bone marrow transplantation. At the begining of this study, we observed that CD57+ T cells as well as CD56+ T cells were abundant at tumour sites in many patients with colorectal cancer. Since all these findings for CD57+ T cells are quite similar to those of extrathymic T cells seen in mice, we investigated how CD57+ T cells are distributed to various immune organs in humans. They were found to be present mainly in the bone marrow and liver, but to be completely absent in the thymus. Similar to the case of extrathymic T cells in mice, they were observed to consist of double‐negative CD48+ subsets as well as single‐positive subsets (preponderance of CD8+ cells), and to contain a considerable proportion of γδ T cells. These features are striking when compared with those of CD57+ T cells, which are characterized by an abundance of CD4+ subsets and αβ T cells. Not only at tumour sites but also in the peripheral blood, some patients with colorectal cancer displayed elevated levels of CD57+ cells. These results suggest that CD57+ T cells may be of extrathymic origin, possibly originating in the bone marrow and liver, and may be associated with tumour immunity, similar to another extrathymic population of CD56+ T cells in humans.

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Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains [see comments]

Cited by 30 publications

References 32 publications

IL4 production and increased CD30 expression by a unique CD8⁺ T‐cell subset in B‐cell chronic lymphocytic leukaemia

IL4 production and increased CD30 expression by a unique CD8⁺ T‐cell subset in B‐cell chronic lymphocytic leukaemia

TCR Vβ repertoire analysis in CD56⁺ CD16^dim/− T‐cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes

Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer

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Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains [see comments]

Cited by 30 publications

References 32 publications

IL4 production and increased CD30 expression by a unique CD8+ T‐cell subset in B‐cell chronic lymphocytic leukaemia

IL4 production and increased CD30 expression by a unique CD8+ T‐cell subset in B‐cell chronic lymphocytic leukaemia

TCR Vβ repertoire analysis in CD56+ CD16dim/− T‐cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes

Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer

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IL4 production and increased CD30 expression by a unique CD8⁺ T‐cell subset in B‐cell chronic lymphocytic leukaemia

IL4 production and increased CD30 expression by a unique CD8⁺ T‐cell subset in B‐cell chronic lymphocytic leukaemia

TCR Vβ repertoire analysis in CD56⁺ CD16^dim/− T‐cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes