Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia.
OBJECTIVE
During an ongoing immune response, cytokines produced by T helper types 1 (Th1) and 2 (Th2) together with T cytotoxic types 1 (Tc1) 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).


METHODS
We analyzed 61 blood samples from 45 children with B cell precursor ALL and 16 healthy children. Interleukin(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 CD4+ 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 20.1 +/- 10.3 respectively) in 15 healthy controls (P < 0.0001). Although both CD45RA+/CD4+ and CD45RA+/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.


CONCLUSIONS
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).
Zhang
X L
XL
Department of Pediatrics, Mie University School of Medicine, Japan.
Komada
Y
Y
Chipeta
J
J
Li
Q S
QS
Inaba
H
H
Azuma
E
E
Yamamoto
H
H
Sakurai
M
M
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D007376:Interleukin-2; D008222:Lymphokines; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens