Fever-mediated Th2-skewing of activated CD4 T cell programming is IL4 independent but Notch dependent (A). Up-regulation of Gata3 in wild-type (WT) and IL4−/− NCD4 cells activated at 37 °C or 39 °C with anti-CD3+anti-CD28 for 6 h. Mean ± SE; n = 3. UNS: unstimulated. (B and C) IL13 (B) and IFNg (C) levels in culture supernatants during recall response of NCD4 T cells from IL4−/− mice primed at 37 °C or 39 °C. Mean ± SE; n = 3. unst: unstimulated. (D) Change in Gata3, Hes1, and Hey1 mRNA levels of NCD4 T cells activated at 37 °C or 39 °C for 6 h. uns, unstimulated NCD4 T cells. Mean ± SE; n = 3. (E) Change in gata3 and Hes1 mRNA levels of NCD4 T cells activated at 37 °C or 39 °C in the presence or absence of Notch inhibitor DAPT for 6 h. unst, unstimulated NCD4 T cells. Mean ± SE; n = 3. (F and G) IL13 (F) and IFNg (G) levels in culture supernatants during recall response of NCD4 T cells activated at 37 °C or 39 °C in the presence or absence of DAPT. Mean ± SE; n = 3. (H and I). Change in Gata3 (H) and Hes1 (I) mRNA levels of NCD4 T cells from WT and Notch1−/− (knockout; KO) mice activated at 37 °C or 39 °C in the presence or absence of Caps for 6 h. uns, unstimulated NCD4 T cells. Mean ± SE; n = 3. ns, not significant, *P < 0.05; **P < 0.001; ***P < 0.0001.