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Control of homeostatic proliferation by regulatory T cells
Shiqian Shen, … , Maria A. Curotto de Lafaille, Juan J. Lafaille
Shiqian Shen, … , Maria A. Curotto de Lafaille, Juan J. Lafaille
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3517-3526. https://doi.org/10.1172/JCI25463.
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Research Article Immunology Article has an altmetric score of 3

Control of homeostatic proliferation by regulatory T cells

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Abstract

Homeostatic proliferation of T cells leads to the generation of effector/memory cells, which have the potential to cause harm to the host. The role of Tregs in the control of homeostatic proliferation is unclear. In this study we utilized mice that either harbor or lack Tregs as recipients of monoclonal or polyclonal T cells. We observed that while Tregs completely prevented cell division of T cells displaying low affinity for self ligands, they had a less marked, albeit significant, effect on cell cycle entry of T cells displaying higher affinity. The presence of Tregs resulted in a lower accumulation of T cells, enhanced apoptosis, and impaired differentiation to a cytokine-producing state. We conclude that Tregs play a major role in the control of homeostatic proliferation.

Authors

Shiqian Shen, Yi Ding, Carlos E. Tadokoro, Danyvid Olivares-Villagómez, Marlin Camps-Ramírez, Maria A. Curotto de Lafaille, Juan J. Lafaille

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Figure 1

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Control of homeostatic proliferation correlates with the presence of Tre...
Control of homeostatic proliferation correlates with the presence of Tregs in MBP/R+ and OVA/R+ mice. (A) Presence of naturally occurring Tregs in OVA/R+ and MBP/R+ mice but not in OVA/R– and MBP/R– mice. Lymph node cells from 4- to 7-week-old OVA/R–, OVA/R+, MBP/R–, and MBP/R+ mice were stained with anti-CD4 and anti-Foxp3, gated on live lymphocytes. Numbers indicate frequency among total live lymphocytes. Data are representative of 10 mice. (B) OVA/R–, but not OVA/R+ mice, support homeostatic proliferation of MBP-specific T cells, whereas MBP/R–, but not MBP/R+ mice, support homeostatic proliferation of OVA-specific T cells. Top row: 1 × 107 CFSE-labeled splenocytes from H-2d/u Thy1.1 MBP/R– donor mice were transferred into H-2d/u Thy1.2 OVA/R– (left) or H-2d/u Thy1.2 OVA/R+ (right) recipient mice; 12 days after transfer, recipients were sacrificed and single-cell suspensions were made from brachial, inguinal, and axillary lymph nodes. Plots show cells gated on Thy1.1+ anti–MBP TCR (3H12+) cells. Data are representative of 4 mice. Bottom row: 1 × 107 CFSE-labeled splenocytes from H-2d/u Thy1.1 OVA/R– donor mice were transferred into H-2d/u Thy1.2 MBP/R– (left) or H-2d/u Thy1.2 MBP/R+ (right) recipient mice; 12 days after transfer, recipients were sacrificed, and single-cell suspensions were made from brachial, inguinal, and axillary lymph nodes. Plots show cells gated on Thy1.1+KJ1.26+ cells. Data are representative of 4 mice.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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