Regulatory T-cell and T-helper 17 balance in chronic lymphocytic leukemia progression and autoimmune cytopenias.
The reasons for progression and autoimmune cytopenias (AIC) in chronic lymphocytic leukemia (CLL) are not entirely clear, with previous studies suggesting a role for regulatory T-cells (Treg). In this study we prospectively studied Treg (CD3+CD4+CD25highCD127low), interleukin-10 (IL-10) producing Treg and T-helper 17 (Th17) (CD3+CD4+IL-17+) cells in 40 treatment-naive patients with CLL. The percentage of Th17 and not Treg cells was significantly higher in the AIC cohort than in those without AIC (p<0.0001). The Treg:Th17 ratio was skewed in favor of Th17 in the AIC cohort (p=0.02). Th17 cells are responsible for AIC of CLL. Analysis of lymph-node aspirates showed that the percentage of Treg and IL-10 expression in Treg and not Th17 was significantly higher than in peripheral blood (p<0.01). Treg cells play a major role in the microenvironment where disease progression occurs. This shows the importance of maintaining the Treg:Th17 equilibrium, for imbalance leads to CLL progression or AIC.
a Department of Internal Medicine , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Deepesh P
DP
Lad
a Department of Internal Medicine , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Subhash
S
Varma
b Department of Hematology , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Neelam
N
Varma
b Department of Hematology , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Man Updesh Singh
MU
Sachdeva
b Department of Hematology , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Parveen
P
Bose
a Department of Internal Medicine , Post Graduate Institute of Medical Education and Research , Chandigarh , India.
Pankaj
P
Malhotra
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D015551:Autoimmunity; D015415:Biomarkers; D016022:Case-Control Studies; D060833:Cellular Microenvironment / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010198:Pancytopenia / Q000097:blood / Q000276:immunology*; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D015415:Biomarkers; D016753:Interleukin-10
Autoimmune cytopenia; T-helper 17; chronic lymphocytic leukemia; regulatory T-cells