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Published on: June 22, 2016
Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia
Krzysztof Giannopoulos1, Michael Schmitt, Malgorzata Kowal
1Department of Internal Medicine III, University of Ulm, Ulm, Germany. krzysztof.giannopoulos@alumni.uni-ulm.de
Insights
Immune system dysfunction in B-cell chronic lymphocytic leukemia (B-CLL) is linked to increased T regulatory cells (Treg). Higher Treg frequencies in B-CLL patients correlate with reduced immune responses to tumor and viral antigens, indicating a key immunosuppression mechanism.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- B-cell chronic lymphocytic leukemia (B-CLL) is characterized by immune dysregulation, including immunodeficiency and autoimmunity.
- The precise role of T regulatory lymphocytes (Treg) in the compromised immune status of B-CLL patients remains incompletely understood.
Purpose of the Study:
- To investigate the frequency and functional impact of T regulatory lymphocytes (Treg) expressing FOXP3 in B-CLL patients.
- To assess the correlation between Treg levels and disease progression, prognostic markers, and immune responses against tumor and viral antigens.
Main Methods:
- Flow cytometry was used to quantify CD4+CD25hi FOXP3+ Treg cells in 80 B-CLL patients and healthy volunteers (HV).
- Treg frequencies were analyzed in relation to B-CLL disease stages (Binet classification), prognostic markers (ZAP-70, CD38, HLA-G), and serum TNF levels.
- T-cell immune responses against tumor-associated antigens (survivin, fibromodulin, RHAMM) and influenza matrix protein were evaluated.
Main Results:
- B-CLL patients exhibited significantly higher frequencies of Treg compared to HV, with levels increasing alongside disease progression (Stage A, B, C).
- Treg frequency correlated positively with serum TNF levels but showed no correlation with ZAP-70, CD38, or HLA-G.
- Elevated Treg frequencies were associated with diminished T-cell responses against both viral and tumor-associated antigens.
Conclusions:
- This study confirms increased Treg frequencies in B-CLL patients, which rise with disease progression.
- T regulatory lymphocytes play a critical role in mediating immunosuppression within the B-CLL microenvironment.
- The findings highlight Treg as a significant factor contributing to the impaired immune surveillance observed in B-CLL.
Abstract:
The status of the immune system of patients with B-cell chronic lymphocytic leukemia (B-CLL) is not yet sufficiently characterized. Clinically, B-CLL patients present immunodeficiency increasing along with disease progression and signs of autoimmunity. In the current study, we evaluated the expression of FOXP3 in CD4+CD25hi T regulatory lymphocytes (Treg) and their influence on immune response against tumor and viral antigens in the complex system of peripheral blood mononuclear cells. In 80 B-CLL patients, the frequency of Treg (CD4+CD25hi FOXP3+) cells was significantly higher in B-CLL patients when compared to healthy volunteers (HV) and increased with the progression of the disease (median: 8.24% in stage A, 11.24% in stage B and 12.57% in stage C according to the Binet classification). The frequency of Treg showed no correlation with prognostic markers such as ZAP-70, CD38 and HLA-G. Notably, Treg frequency correlated with serum levels of TNF (r(2)=0.45, p=0.001). T-cell immune responses against epitopes derived from the tumor-associated antigens survivin, fibromodulin and RHAMM as well as from the influenza matrix protein were evaluated. Functionally, higher frequencies of Treg correlated with decreased T-cell responses against viral and tumor antigens. In conclusion, we detected higher frequencies of Treg in B-CLL patients than in HV. Furthermore, Treg constitute the crucial mechanism of immunosuppression in B-CLL patients.
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