Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia |
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Authors: | Xao-Li Zhang Yoshihiro Komada James Chipeta Qing-Sheng Li Hiroto Inaba Eiichi Azuma Hatsumi Yamamoto Minoru Sakurai |
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Institution: | (1) Department of Pediatrics, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan e-mail: komda@clin.mdic.mie-u.ac.jp Tel.: +81-59-232-1111 Fax: +81-59-231-5213, JP;(2) Department of Clinical Immunology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan, JP;(3) Department of Pediatrics and Clinical Research Institute, National Mie Chuo Hospital, 2158-5 Myojin-cho, Hisai, Mie 514-1101, Japan, JP |
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Abstract: | Purpose: 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 γ (IFNγ) 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, IFNγ-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 IFNγ) production. Interestingly,
the ability to produce both IL-2 and IFNγ 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).
Received: 12 November 1999 / Accepted: 2 January 2000 |
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Keywords: | Intracellular cytokine pattern Th1/Th2 cell Tc1/Tc2 cell Acute lymphoblastic leukemia |
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