Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia

Purpose: During an ongoing immune response, cytokines produced by T helper types I (Th1) and 2 (Th2) together with T cytotoxic types 1 (Tcl) and 2 (Tc2) are critical to the effectiveness of that response. Dysregulated expansion of one or the other subset may contribute to the impaired function of the T-cell-mediated immune system in cancer patients. In the present study we have investigated whether such dysregulation might exist in children with acute lymphoblastic leukemia (ALL). Il;Methods: We analyzed 61 blood samples from 45 children with B cell precursor ALL and 16 healthy children. Interlukin (IL)-2, IL-4, and interferon gamma (IFN gamma) production of their respective purified CD4(+) and CD8(+) T cells were assessed at the single-cell level by intracellular-cytokine-staining flow cytometry. Results: At the time of diagnosis, IL-2-producing cell populations in CD3(+) and CD8(+) T cells were reduced below the normal range in 31 of 44 (70.5%) and 23 of 38 (60.5%) cases respectively. Similarly, IFN gamma-producing cell populations in CD4(+) and CD8(+) T cells decreased in 17 of 44 (38.6%) and 18 of 38 (47.4%) cases respectively. Conversely cell populations capable of IL-4 production in CD4(+) and CD8(+) T cell subsets were increased in 13 of 30 (43.3%) and 15 of 30 (50.0%) cases respectively. Therefore, the Th1-to-Th2 and Tc1-to-Tc2 ratios (1.6 +/- 2.2 and 7.7 +/- 6.7 respectively) were significantly lower in peripheral blood T cells of ALL patients (n = 30) than those (6.0 +/- 2.9 and 30.1 +/- 10.3 respectively) in 15 healthy controls (P < 0.0001). Although both CD45RA(+)/CD4(+) and CD35RA(+)/ CD8(+) cells significantly increased in 43 ALL patients (P < 0.05), there existed no apparent correlation between CD45 isoform expression and cytokine (IL-2 and IFN gamma) production. Interestingly, the ability to produce both IL-2 and IFN gamma was recovered in 8 cases examined, after complete remission had been achieved. Conclusion: These observations suggest that, in both CD4(+) and CD8(+) T cells of ALL patients, there is a dysregulation in the functionality of Th1 (Tc1) and Th2 (Tc2) cells with a gross reduction of Th1 (Tc1) cell populations and an expansion in Th2 (Tc2).