Circulating T cells in patients with untreated acute myelogenous leukemia are heterogeneous and can be activated through the CD3/TCR complex.
T lymphocyte defects may contribute to the immune insufficiency seen in acute myelogenous leukemia (AML). We therefore characterized the T cell system for untreated AML patients. T lymphocyte subsets were analyzed by flow cytometry for 45 AML patients. The in vitro interferon-gamma (IFNgamma) release in response to stimulation with anti-CD3 plus anti-CD28 in the presence of autologous AML cells was examined for 31 patients. The majority of circulating lymphocytes were CD3(+)T cells, and CD19(+)B cells usually constituted < 10% of the lymphocytes. Most T cells expressed the alphabeta T cell receptor (TCRalphabeta(+)), and only a minority of the cells was TCRgammadelta(+). Both CD4(+) and CD8(+)T cells were detected, the CD4:CD8 ratio showed a wide variation but was generally >1.0. The majority of CD4(+) and CD8(+)T cells were CD45RA(+) cells. The T cells could be stimulated to release IFNgamma in response to anti-CD3 plus anti-CD28 ligation even in the presence of excess autologous AML blasts, and for a subset of patients (6 of 27) these IFNgamma levels could be further increased by the novel protein kinase C (PKC) agonist PEP005. In conclusion, circulating T cells in patients with untreated AML are mainly CD4(+) or CD8(+) TCRalphabeta(+); both CD45RA(+) and CD45R0(+) can be detected, and these cells can be activated through the CD3/TCR complex even in the presence of excess AML cells. For a subset of patients T cell responsiveness can be further increased by targeting PKC and these data therefore suggest that T cell function is not inhibited in AML patients.
Ersvaer
Elisabeth
E
University of Bergen and Haukeland University Hospital, Institute of Medicine, Bergen, Norway. elisabeth.ersvar@med.uib.no
Hampson
Peter
P
Wendelbo
Øystein
Ø
Lord
Janet M
JM
Gjertsen
Bjørn Tore
BT
Bruserud
Øystein
Ø
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells; D017252:CD3 Complex / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C