Phenotypic and functional characterization of the host immune compartment of chronic myeloid leukaemia patients in complete haematological remission

The role of the host immune compartment in the control of chronic myeloid l eukaemia (CML) has been suggested by numerous biological and clinical evide nce. In the present study, the phenotypic and functional machinery of both T and cytotoxic lymphocytes was evaluated in a series of CML patients in co mplete haematological, and frequently also in cytogenetic, remission after treatment with interferon (IFN) alpha or hydroxyurea, and compared with the profile observed in patients at diagnosis and in normal controls. in parti cular, the lymphocyte subset distribution, the cytotoxic activity and the i ntracellular production of tumour necrosis factor (TNF)alpha and IFN gamma by CD4(+), CD8(+) and CD56(+) cells were investigated, CML patients in comp lete haematological remission showed a normalized CD4/CD8 T-cell subset dis tribution, as well as a restored spontaneous and interleukin 2 (IL-2) induc ed cytotoxic function compared with the pattern observed at diagnosis, This was associated with a significantly increased proportion of activated CD4( +) lymphocytes (CD25(+)). TNF alpha and IFN gamma production by CD4(+), CD8 (+) and CD56(+) lymphocytes was significantly enhanced compared with that o f patients at diagnosis. However, the values were lower than those of norma l controls. These results indicate that, in contrast to the observations at presentation, CML patients, at the time of the best possible response to t reatment, show a normalized T-cell subset distribution associated with an a ctivated CD4 T-cell compartment and a restored cytotoxic activity, In addit ion, they also show a markedly increased intracellular cytokine production by the lymphoid populations that play an important role in the process of s pecific tumour recognition. The design of therapeutic strategies aimed at s timulating the host immune compartment finds a further rationale for CML, p atients responsive to treatment with both IFN alpha and hydroxyurea.