Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells.
BACKGROUND
Several observations suggest that immunological events early after chemotherapy, possibly during the period of severe treatment-induced cytopenia, are important for antileukemic immune reactivity in acute myeloid leukemia (AML). We therefore investigated the frequencies of various T cell subsets (TC1, TH1, TH17) and CD25+ FoxP3+ TREG cells in AML patients with untreated disease and following intensive chemotherapy.


RESULTS
Relative levels of circulating TC1 and TH1 cells were decreased in patients with severe chemotherapy-induced cytopenia, whereas TH17 levels did not differ from healthy controls. Increased levels of regulatory CD25+ FoxP3+ T cells were detected in AML patients with untreated disease, during chemotherapy-induced cytopenia and during regeneration after treatment. TH17 and TH1 levels were significantly higher in healthy males than females, but this gender difference was not detected during chemotherapy-induced cytopenia. Finally, exogenous IL17-A usually had no or only minor effects on proliferation of primary human AML cells.


CONCLUSIONS
We conclude that the effect of intensive AML chemotherapy differ between circulating T cell subsets, relative frequencies of TH17 cells are not affected by chemotherapy and this subset may affect AML cells indirectly through their immunoregulatory effects but probably not through direct effects of IL17-A.
Ersvaer
Elisabeth
E
Institute of Medicine, University of Bergen, Bergen, Norway. elisabeth.ersvar@med.uib.no
Liseth
Knut
K
Skavland
Jørn
J
Gjertsen
Bjørn Tore
BT
Bruserud
Øystein
Ø
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006262:Health; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology*; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured; D055815:Young Adult
D000970:Antineoplastic Agents; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit