Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia.
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.
Giannopoulos
Krzysztof
K
Department of Internal Medicine III, University of Ulm, Ulm, Germany. krzysztof.giannopoulos@alumni.uni-ulm.de
Schmitt
Michael
M
Kowal
Malgorzata
M
Wlasiuk
Paulina
P
Bojarska-Junak
Agnieszka
A
Chen
Jinfei
J
Rolinski
Jacek
J
Dmoszynska
Anna
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D010446:Peptide Fragments; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D007371:Interferon-gamma; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human