Signaling molecules and cytokine production in T cells of patients with B-cell chronic lymphocytic leukemia (B-CLL): comparison of indolent and progressive disease.
T-cell dysfunction in B-CLL patients might be attributed to altered expression of components of the TCR/CD3 complex and associated intracellular tyrosine kinases. Four-color flow cytometry was applied to the expression of these molecules as well as the T-cell regulatory cytokines (IFN-gamma and IL-4) in B-CLL patients with indolent and progressive disease. Intracellular levels [mean fluorescent intensity (MFI)] of IFN-gamma and IL-4 in both CD4 and CD8 T cells of both patient groups were significantly higher than in healthy donors. Absolute number of IL-4 producing CD4 T cells in patients with indolent was significantly higher than in healthy donors. The expression level (MFI) of the CD3-zeta chain was higher in patients than in normal donors as well as ZAP-70 in patients with indolent disease as compared to healthy donors and progressive patients. No significant difference was noted in the expression of p56lck, p59fyn, and PI3-kinase between healthy donors and patients or between the patient subgroups. The results indicate multiple T-cell abnormalities especially in indolent-stage B-CLL suggesting a state of chronic and aberrant activation. This information might be of significance when studying the immunobiology of B-CLL as well as developing new therapeutic approaches.
Kiaii
Shahryar
S
Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
Choudhury
Aniruddha
A
Mozaffari
Fariba
F
Kimby
Eva
E
Osterborg
Anders
A
Mellstedt
Håkan
H
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines