Homeostatic T cell proliferation in a T cell-dendritic cell coculture system.
Naive T cells do not proliferate in normal individuals in the absence of antigen stimulation, but they proliferate spontaneously when T cells are severely depleted. We show here that coculture of syngeneic dendritic cells (DC) with naive T cells expressing a single T cell receptor also results in T cell proliferation in the absence of foreign antigen. As in lymphopenic mice, where T cell proliferation depends upon DC, this response in the coculture system requires interaction of the T cells' T cell receptor with self-peptide-MHCs on DC. This in vitro proliferation also requires soluble factors, including IL-15 secreted by DC, and can be inhibited potently by cell-cell contact with CD4+CD25+ regulatory T cells. The coculture system described may illuminate mechanisms that maintain stable numbers of T cells in normal individuals.
Ge
Qing
Q
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Palliser
Deborah
D
Eisen
Herman N
HN
Chen
Jianzhu
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis; D019409:Interleukin-15 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology*
D016207:Cytokines; D018398:Homeodomain Proteins; D019409:Interleukin-15; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein