Intracellular T cell cytokines in patients with B cell chronic lymphocytic leukaemia (B-CLL).
Analysis of cytokine production is a tool to functionally characterise T cells. In this study, spontaneous and polyclonal activation induced cytokine production in T cells were assessed by flow cytometry in patients with B-CLL. Patients with progressive disease had a significantly increased number of T cells spontaneously producing IL-2, IL-4 and GM-CSF as compared to healthy donors and patients with non-progressive CLL, which was not the case for TNF-alpha and IFN-gamma producing T cells. However, no difference in the frequency of T cells producing these cytokines was seen comparing patients with non-progressive disease to control donors. Polyclonal activation of B-CLL T cells in vitro induced an increased proportion of T cells producing these five cytokines in patients as well as in control donors, indicating that T cells in CLL patients might have a relatively well preserved functional capacity. However, the increase in GM-CSF, TNF-alpha and IL-4 producing T cells was more marked in CLL patients than in controls. Furthermore, following activation, a higher frequency of cytokine-producing T cells was noted in patients with progressive disease as compared to those with non-progressive disease. The augmented number of cytokine-producing T cells in CLL may indicate an up-regulated capability of T cells to secrete cytokines, especially in patients with progressive CLL. The increased production of the T cell derived cytokines GM-CSF, TNF-alpha, IL-4 and IL-2 is interesting, as these cytokines have previously been shown to support growth of B-CLL leukaemic cells in vitro and as T cells might specifically recognise the autologous leukaemic B cells in vivo. The findings may suggest a role for T cells in the pathogenesis of B-CLL.
Rossmann
Eva D
ED
Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
Lewin
Nongnit
N
Jeddi-Tehrani
Mahmood
M
Osterborg
Anders
A
Mellstedt
Håkan
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor