Feedback regulation of T cell development in the thymus.
Recent findings suggest that mature T cells in the thymus may regulate the growth and differentiation of immature thymocytes. Here we use mathematical modeling and computer simulations to identify the thymocyte subsets that might serve as targets for regulation, and the processes that might be affected by regulation. Our results suggest that thymocyte development is subject to regulation through two feedback loops: mature CD4+ T cells exert a positive feedback on the single positive CD4+8- thymocyte compartment, by reducing CD4+8- cell death and possibly accelerating the differentiation of CD4+8+ thymocytes into CD4+8- thymocytes; they may also exert a negative feedback on the double-positive CD4+8+ thymocyte compartment, by reducing the proliferation or accelerating the maturation of these cells.
Mehr
R
R
Theoretical Division, Los Alamos National Laboratory, NM 87545, USA. ramit@t10.lanl.gov
Perelson
A S
AS
Fridkis-Hareli
M
M
Globerson
A
A
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002455:Cell Division; D003198:Computer Simulation; D005246:Feedback; D006801:Humans; D008433:Mathematics; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*