Autocrine IL-2 production drives divergent responses in CD4 ⁺ and CD8 ⁺ T cells. Chimeric mice were generated using BM from WT (CD45.1⁺) and CD4^creRosa^IL-2 (CD45.2⁺) at varying ratios. n = 4–6, pooled from two independent experiments. (A) Schematic of experimental outline. (B) Frequency of CD4⁺ and CD8⁺ Tconv cells (as percentage of viable splenocytes) or CD4⁺ Tregs (as percentage of total CD4⁺ T cells). (C) Frequency of splenocyte population derived from CD4^creRosa^IL-2 (CD45.2⁺) BM after reconstitution versus frequency of input BM. (D) Frequency of naive (CD44^loCD62L^hi), Teff (CD44^hiCD62L^lo), or Tcm (CD44^hiCD62L^hi) cells derived from CD4^creRosa^IL-2 (CD45.2⁺) in spleen. (E) CD4⁺CD25⁻ or CD8⁺ T cells from WT and CD4^creRosa^IL-2 mice were adoptively transferred at equal ratios into immunocompetent congenic mice. Serum IL-2 levels are shown for control mice and mice that received CD4 or CD8 T cells (n = 4–5). (F) Frequency of donor cells among total CD4⁺ Tconv cells 2 wk after transfer; n = 4. (G) Frequency of donor cells among total CD8⁺ Tconv cells and Ki67 expression 2 wk after transfer; n = 5. (H) pSTAT5 and pSTAT3 in freshly isolated T cells. F minus one level indicated by dashed line. (I) Mean fluorescence intensity (MFI) and percentage of cells expressing CD25 and CD25/CD132 (common γ chain) MFI ratio on CD4⁺ Treg, CD4⁺ Tconv, and CD8⁺ T cells in WT and CD4^Cre Rosa^IL-2 transgenic mice. (J) MFI and percentage of cells expressing CD127 (IL-7Rα) and CD127/CD132 MFI ratio on CD4⁺ Treg, CD4⁺ Tconv, and CD8⁺ T cells in WT and CD4^Cre Rosa^IL-2 transgenic mice. (K) Upregulation of pSTAT5 in response to cytokine stimulation in CD4⁺ Treg, naive CD4⁺ Tconv, and CD8⁺ T cells. (L) Upregulation of pSTAT3 in response to cytokine stimulation in CD4⁺ Treg, naive CD4⁺ Tconv, and CD8⁺ T cells. (M) Fold-change in MFI of receptor expression in CD45.2⁺ cells to CD45.1⁺ cells in chimeric mice generated as 50% CD4^creIl2^fl/fl or CD4^wtIl2^fl/fl (CD45.2⁺):50% WT (CD45.1⁺). Significance was tested by paired t test (F and G) or Sidak’s multiple comparison test on two-way ANOVA (H–M).