Control of homeostatic proliferation by regulatory T cells
J. Clin. Invest. Shiqian Shen, et al. 115:3517 doi:10.1172/JCI25463 [Go to this article.]

Figure 3
The mere presence of memory T cells is not sufficient to prevent homeostatic proliferation of naive T cells bearing a different TCR specificity. (A) 1 × 10⁷ splenocytes from H-2^d/u OVA/R^– mice were transferred into nontransgenic H-2^d/u RAG-1^–/– recipient mice (n = 4). After 10–12 weeks, the transferred CD4⁺ cells acquired a CD44^hi phenotype consistent with memory T cells. Filled histogram: KJ1.26⁺ cells before transfer; open histogram: KJ1.26⁺ cells parked in nontransgenic H-2^d/u RAG-1^–/– recipient mice. (B) Subsequently, 1 × 10⁷ CFSE-labeled splenocytes from H-2^d/u MBP/R^– mice were transferred into the same recipients. Twelve days after the second transfer, single-cell suspensions of lymph node cells from the recipient mice were made and stained with anti-CD4, anti-CD44, and the anti–MBP TCR clonotypic antibody 3H12 for FACS analysis. The left panel shows the gate on MBP-specific T cells, and the right panel shows the highly efficient generation of MBP-specific memory T cells (CD44^hi CFSE^lo). (C) Adoptive transfer of Tregs. 2.5 × 10⁶ purified CD4⁺CD25⁺ or CD4⁺CD25^– T cells from H-2^d/u wild-type mice were transferred into H-2^d/u MBP/R^– recipient mice. Three days later, 1 × 10⁷ CFSE-labeled splenocytes from H-2^d/u OVA/R^– were transferred into the same recipients, and 12 days after the second transfer, single-cell suspensions of lymph node cells from the recipient mice were prepared and stained with anti-CD4, anti–KJ1-26 (clonotypic antibody for the OVA-specific TCR), and anti-TCRβ antibodies. Plots show cells gated on CD4⁺KJ1-26⁺TCRβ⁺ cells. A time gate was also used to allow the display of the same number of CD4⁺KJ1-26⁺ donor-derived cells in each overlaid histogram. Data are representative of 3 mice per group.