Intracellular cytokine analysis of interferon-? in T cells of patients with chronic myeloid leukemia

JM Aswald, JH Lipton, HA Messner - Cytokines, cellular & …, 2002 - Taylor & Francis
JM Aswald, JH Lipton, HA Messner
Cytokines, cellular & molecular therapy, 2002Taylor & Francis
The role of T cells in eradicating leukemic cells has been well demonstrated for chronic
myeloid leukemia (CML). Type 1 (T1) T-cell cytokines play a major role in this anti-leukemic
immune effect. Studies in cancer patients have demonstrated a decreased T1 cytokine
production, measured by enzyme-linked immunosorbent assay (ELISA), in cultures of
peripheral blood mononuclear cells. This observation of malignancy-related suppressed T1
cytokines also occurs in untreated chronic-phase (CP) CML, raising the question of the …
The role of T cells in eradicating leukemic cells has been well demonstrated for chronic myeloid leukemia (CML). Type 1 (T1) T-cell cytokines play a major role in this anti-leukemic immune effect. Studies in cancer patients have demonstrated a decreased T1 cytokine production, measured by enzyme-linked immunosorbent assay (ELISA), in cultures of peripheral blood mononuclear cells. This observation of malignancy-related suppressed T1 cytokines also occurs in untreated chronic-phase (CP) CML, raising the question of the influence of different CML treatment regimens on this immunosuppression. Intracellular flow cytometry (ICF) has facilitated the evaluation of cytokines on a single-cell level. This study analyzed T1 (interferon-γ) cytokine production in purified peripheral blood T cells by ICF, comparing different therapy approaches for CML. Twenty-one newly diagnosed CP CML patients were compared with 24 patients treated with interferon-alpha (IFN-α) and to 30 allogeneic bone marrow transplant (BMT) recipients (BCR-ABL negative by reverse-transcriptase polymerase chain reaction, and free of, or having only limited graft-versus-host disease at the time of study). Thirty-seven healthy controls were included. Our results showed a significantly decreased T-cell IFN-γ synthesis in CP CML patients in relation to healthy controls (P=0.0007). Treatment with IFN-α resulted in a shift from immunosuppression -- documented for the group of untreated patients -- to immunopotentiation, with an increase of T-cell IFN-γ production (P=0.0266). Notably, BMT enhanced IFN-γ production of T cells to a level not only exceeding untreated patients (P<0.0001) but also healthy volunteers (P<0.0001). The observation of T1 cytokine up-regulation with IFN-α therapy indicates that enhanced T-cell function may be achievable in patients with CML, even in the absence of an allo-response.
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