Fig. 2

CD4⁺ T cell is altered in childhood cancer survivors (CCS) treated with TBI (total body irradiation)/HSCT (hematopoietic stem cell transplant). a. Schematic representation of intracellular signaling involved in polarized activation in T cells. b. Representative FACS dot plot of CD4⁺ cells producing interferon (IFN)-γ (X-axis) or interleukin (IL)-4 (Y-axis) in CCS treated with TBI/HSCT (bottom) or no irradiation (non-IRR, top). The frequency of CD4⁺ cells producing IFN-γ was higher in CCS treated with TBI/HSCT compared to non-IRR CCS (p < 0.01), with no difference in CD4⁺ cells producing IL-4 (p = 0.3). c. Representative histograms for phosphorylated p38, phosphorylated ribosomal protein S6 kinase 1 (pS6 k1), phosphorylated c-Jun N-terminal kinase (pJNK), and phosphorylated Akt on Ser473 under resting condition (Rest) and upon mitogen stimulation (Stim). Upon mitogen stimulation, p-p38, pS6k1, pJNK, and pAkt Ser473 were all significantly increased (*p < 0.05, compared to resting condition) in CD4⁺ cells in both groups (n = 10 in each group). Higher resting phosphorylation levels of p38 and S6 k1 were observed in CD4⁺ cells from CCS treated with TBI (p = 0.02 and p = 0.04 respectively). d. Plasma levels of Th1 cytokines including interferon (IFN)-γ and tumor necrosis factor (TNF)-α were significantly elevated in CCS treated with TBI/HSCT (p < 0.01 and p = 0.04 respectively) whereas interleukin (IL)-10 and IL-13, or IL-2 and IL-12, did not differ between the two groups (p > 0.05)