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The CD3 versus CD7 plot in multicolor flow cytometry reflects progression of disease stage in patients infected with
Seiichiro Kobayashi1, Yamin Tian, Nobuhiro Ohno
1Division of Molecular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Insights
The CD3 versus CD7 plot can indicate disease progression in human T-cell leukemia virus type I (HTLV-I) infected individuals. This profile, combined with proviral load, may help predict disease advancement in asymptomatic carriers.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Adult T-cell leukemia-lymphoma (ATL) is a malignancy of mature T lymphocytes.
- Human T-cell leukemia virus type I (HTLV-I) is the causative agent of ATL and associated myelopathies.
- Identifying markers for disease progression in HTLV-I infection is crucial for patient management.
Purpose of the Study:
- To investigate whether the CD3 versus CD7 expression profile on T cells reflects disease progression in patients with indolent-type ATL and HTLV-I asymptomatic carriers (ACs).
- To evaluate the CD3 versus CD7 plot as a potential indicator for forecasting disease progression in HTLV-I infection.
Main Methods:
- Multi-color flow cytometry was used to analyze peripheral blood mononuclear cells from ATL patients and HTLV-I ACs.
- Cells were sorted using fluorescence-activated cell sorting (FACS).
- Molecular analyses, including inverse long PCR, were performed on sorted cells to assess clonality.
Main Results:
- Patient data, when plotted as D(%) versus L(%), largely segregated into three groups corresponding to ACs, indolent ATL, and acute ATL.
- Clinical disease progression correlated with changes in the CD3 versus CD7 profile during patient follow-up.
- Clonality analysis revealed a dominant clone in both D and L subpopulations in ATL cases and in some ACs, suggesting early clonal expansion.
Conclusions:
- The CD3 versus CD7 expression profile serves as a valuable indicator of disease stage progression in HTLV-I-infected individuals.
- This profile, in conjunction with high proviral load, shows promise as a new biomarker for predicting disease progression in HTLV-I ACs.
Purpose:
In a recent study to purify adult T-cell leukemia-lymphoma (ATL) cells from acute-type patients by flow cytometry, three subpopulations were observed in a CD3 versus CD7 plot (H: CD3(high)CD7(high); D: CD3(dim)CD7(dim); L: CD3(dim)CD7(low)). The majority of leukemia cells were enriched in the L subpopulation and the same clone was included in the D and L subpopulations, suggesting clonal evolution. In this study, we analyzed patients with indolent-type ATL and human T-cell leukemia virus type I (HTLV-I) asymptomatic carriers (ACs) to see whether the CD3 versus CD7 profile reflected progression in the properties of HTLV-I-infected cells.
Experimental Design:
Using peripheral blood mononuclear cells from patient samples, we performed multi-color flow cytometry. Cells that underwent fluorescence-activated cell sorting were subjected to molecular analyses, including inverse long PCR.
Results:
In the D(%) versus L(%) plot, patient data could largely be categorized into three groups (Group 1: AC; Group 2: smoldering- and chronic-type ATL; and Group 3: acute-type ATL). Some exceptions, however, were noted (e.g., ACs in Group 2). In the follow-up of some patients, clinical disease progression correlated well with the CD3 versus CD7 profile. In clonality analysis, we clearly detected a major clone in the D and L subpopulations in ATL cases and, intriguingly, in some ACs in Group 2.
Conclusion:
We propose that the CD3 versus CD7 plot reflects progression of disease stage in patients infected with HTLV-I. The CD3 versus CD7 profile will be a new indicator, along with high proviral load, for HTLV-I ACs in forecasting disease progression.
