Cytokine release by activated T-cells in large granular lymphocytic leukemia associated with autoimmune disorders.
BACKGROUND
Patients with T-cell large granular lymphocytic leukemia (T-LGLL) have a high incidence of autoimmune disorders. The pathogenesis of associated T-LGLL and autoimmune abnormalities is not clear. In this study we have investigated the role of cytokines in the development of immune complications in LGLL.


METHODS
We studied clinical and laboratory features of 15 patients diagnosed with T-LGLL. The patients had various autoimmune disturbances: persistent neutropenia, immune thrombocytopenia, pure red-cell aplasia, Hashimoto's thyroiditis, sicca syndrome, systemic lupus erythemathosus, systemic scleroderma. The T-LGLL cells obtained from these patients were activated by phytohemagglutinin and incubated for 3 days. Using ELISA technique we analysed the release of sIL-2R, IL-4, IL-6, IL-8, IL-10, IL-12 and TNF-alpha in the supernatant.


RESULTS
Cytokine analysis of supernatants obtained from the LGLL T cells stimulated with PHA revealed increased sIL-2R production in 40% (six patients), TNF-alpha - in 47% (seven patients), IL-6 - in 67% (10 patients), IL-10 - in 47% (seven) and IL-8 - in 60% (nine) of patients. Levels of IL-4 and IL-12 were not elevated compared to controls. No correlation was found between LGL count, CD4 versus CD8 expansion, or in the clinical findings of the patients and cytokine release in vitro.


CONCLUSIONS
Our findings showing the potential of LGLL cells for cytokine release in vitro suggests that these cells may play a major role in the immune disturbances observed in large granular lymphocytic leukemia accompanied by autoimmunity features.
Shvidel
Lev
L
Hematology Institute, Kaplan Medical Center, Rehovot, Israel.
Duksin
Chen
C
Tzimanis
Alexandra
A
Shtalrid
Mordechai
M
Klepfish
Abraham
A
Sigler
Erica
E
Haran
Michal
M
Eilat
Eran
E
Berrebi
Alain
A
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned / Q000032:analysis; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D015458:Leukemia, T-Cell / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10