Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells

• DOI: 10.1084/jem.194.7.893
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Alden M. Doyle; Alan C. Mullen; Alejandro V. Vill...; Anne S. Hutchins; Frances A. High; Hubert W. Lee; Craig B. Thompson; Steven L. Reiner
• Keywords: CTLA-4

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion proliferating CD4+ cells. The regulation expression and function ensures that, after ∼3 divisions expansion, most progeny will succumb either proliferative arrest or death over ensuing three divisions. quantitative precision hinges on graded, time-independent induction during first In contrast limits imposed unpolarized cells, helper type 1 (Th1) Th2 effector may be rescued from by interleukin (IL)-12 IL-4 signaling, respectively, allowing appropriately stimulated proceed stage tissue homing. These results suggest cell-autonomous central checkpoint temporally spatially restricted growth dictated nature threat posed host.