CD3 bright lymphocyte population reveal γδ T cells

Wang

Cytometry Part B Clinical

et al. 2006

Background: gd T cells are a rare component of the circulating innate immune system capable of exerting anti-neoplastic activity. This population may be suitable for the adoptive immunotherapy of acute myeloid leukemia (AML). Little is known however, about the frequency and function of circulating gd T cells in AML. The aim of the study was to enumerate peripheral blood gd T cells in patients with AML and explore the feasibility of their use clinically.Methods: We compared the absolute circulating gd T cell levels in 33 AML patients before and after treatment versus 20 healthy volunteers using flow cytometry. The function of gd T cells was assessed by detection of intracelluar interferon-g (IFN-g) and cytotoxicity against leukemic blasts.Results: AML patients with high blast counts prior to induction chemotherapy had marginally decreased gd T cell levels compared with healthy controls: median 38/mL versus 83/mL; P = 0.051. Sequential gd T cell enumeration after induction showed significantly decreased counts in patients with a persistently high blast burden compared to patients with reduced but detectable residual disease (molecular maker or borderline bone marrow infiltration): median 7/mL versus 105/mL; P = 0.008. Patients with residual disease had significantly higher gd T cell counts compared to those retested after they had achieved complete remission (CR); P = 0.0025. In CR, gd T cell counts remained lower than those of healthy individuals: median 33/mL versus 83/mL, P = 0.030. We detected a sharp increase (on average, four-fold higher than values in CR) of gd T cells in patients in very early morphologic or molecular relapse. We also tested the functional properties of gd T cells from patients with AML in CR. Flow cytometric assessment of IFN-g revealed similar numbers of gd T cells expressing the T1 cytokine compared with healthy controls. We also showed that gd T cells were able to kill leukemic target cells in vitro.Conclusion: Flow cytometric assessment of gd T cells in patients with AML revealed quantitative shifts with respect to disease status. Our data suggest that gd T cells warrant further investigation as potential therapeutic agents. q

Section: Flow Cytometric Assessment Of CD T Cells In Amlsupporting

confidence: 64%

“…Effector gd T cells were freshly isolated from PB by immunomagnetic separation as described above, and stained brightly with anti-CD3-FITC (54). Postseparation aliquots immunolabeled with TCRg/d-PE were assessed by flow cytometry for purity.…”

Section: Conditions For Live-cell Imagingmentioning

confidence: 99%

Flow cytometric assessment of autologous γδ T cells in patients with acute myeloid leukemia: Potential effector cells for immunotherapy?

Wang

Cytometry Part B Clinical

et al. 2006

The Journal of Immunology

“…Previous studies on differential CD3 expression in the various T cell subsets have provided fragmented evidence (15,16). To our knowledge, our present study investigated a critical issue with depth: we tested both mouse and human samples; we examined a wide range of T cell subsets; and, perhaps most importantly, we used an unbiased approach for flow cytometry data analysis.…”

Section: Discussionmentioning

confidence: 99%

“…During the last 10 y, Lambert and Genin (15) and El Hentati et al (16) (17). The present study sought to: 1) define, by means of unsupervised analysis of flow cytometry data, whether CD3 heterogeneous expression levels occur in T cell subsets isolated from mice and humans; and 2) evaluate the biological impact of CD3 expression heterogeneity on anti-CD3 treatment in vivo.…”

Section: Foxp3mentioning

confidence: 99%

Heterogeneous CD3 Expression Levels in Differing T Cell Subsets Correlate with the In Vivo Anti-CD3–Mediated T Cell Modulation

Valle

Barbagiovanni

Jofra³

et al. 2015

The tolerogenic anti-CD3ε monoclonal Abs (anti-CD3) are promising compounds for the treatment of type 1 diabetes. Anti-CD3 administration induces transient T cell depletion both in preclinical and in clinical studies. Notably, the said depletion mainly affects CD4+ but not CD8+ T cells. Moreover, type 1 diabetes reversal in preclinical models is accompanied by the selective expansion of CD4+Foxp3+ T regulatory (Treg) cells, which are fundamental for the long-term maintenance of anti-CD3–mediated tolerance. The mechanisms that lead to this immune-shaping by affecting mainly CD4+ T effector cells while sparing CD4+Foxp3+ Treg cells have still to be fully elucidated. This study shows that CD3 expression levels differ from one T cell subset to another. CD4+Foxp3− T cells contain higher amounts of CD3 molecules than do CD4+Foxp3+ and CD8+ T cells in both mice and humans. The said differences correlate with the anti-CD3–mediated immune resetting that occurs in vivo after anti-CD3 administration in diabetic NOD mice. Additionally, transcriptome analysis demonstrates that CD4+Foxp3+ Treg cells are significantly less responsive than are CD4+Foxp3− T cells to anti-CD3 treatment at a molecular level. Thus, heterogeneity in CD3 expression seems to confer to the various T cell subsets differing susceptibility to the in vivo tolerogenic anti-CD3–mediated modulation. These data shed new light on the molecular mechanism that underlies anti-CD3–mediated immune resetting and thus may open new opportunities to improve this promising treatment.

Cytometry Part B Clinical

“…Indeed, cdT cells do express higher levels of CD3 than abT cells (30)(31)(32)(33) though CD3bright T cells do not include all cdT cells. Peripheral cd T cells have restricted diversity.…”

mentioning

confidence: 99%

Variability of CD3 membrane expression and T cell activation capacity

Hentati

Gruy

Iobagiu

et al. 2009

Self Cite

Background: abT cells have a wide distribution of CD3 membrane density. The aim of this article was to evaluate the significance of the CD3 differential expression on T cell subsets. Analysis was performed on healthy donors and renal transplant patients by flow cytometry. The results obtained are: (1) CD3 expression was widely distributed (CV 5 38.3 6 3.1 to 43 6 2.3%). (2) The CD4, CD8, CD45 and forward scatter were similarly distributed. (3) The diversity of CD3 expression was directly related to the clonotypes: c9, non c9 from cdT cells and Vb clonotype from abT cells (e.g., Vb3FITC 7,980 6 1,628 Vb8PE: Vb20-FITC 11,768 6 1,510). (4) Using a computer simulation, we could confirm differential kinetics of T cell activation according to the initial parameters. Finally, in vitro activation was significantly higher on Vb8 and Vb9 (high CD3) compared with Vb2 and Vb3 (low CD3, P 5 0.040-0.0003).