Circulating T cells in patients with untreated acute myelogenous leukemia are heterogeneous and can be activated through the CD3/TCR complex

Abstract

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-γ (IFNγ) 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 αβ T cell receptor (TCRαβ⁺), and only a minority of the cells was TCRγδ⁺. 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 IFNγ 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 IFNγ 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⁺ TCRαβ⁺; 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.

Keywords:

• CYTOPENIA
• T LYMPHOCYTES
• CHEMOTHERAPY
• CYTOKINES
• AML