Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation.
In defense of the host, the immune system must often raise an effective cytotoxic T lymphocyte (CTL) response from a small number of clonal precursors. The degree to which activation stimuli regulate the expansion and differentiation of naïve CTLs, however, remains unknown. Using an engineered antigen-presenting cell (APC) system that allows control over antigenic stimulation, we studied the signaling duration requirements for priming and clonal expansion of naïve CTLs. We found that naïve CTLs become committed after as little as 2 h of exposure to APCs and that their subsequent division and differentiation can occur without the need for further antigenic stimulation of the daughter cells, whether priming is in vitro or in vivo. These data show that after a brief interaction with stimulatory APCs, naïve CTLs initiate a program for their autonomous clonal expansion and development into functional effectors.
van Stipdonk
M J
MJ
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive San Diego, CA 92121, USA.
Lemmens
E E
EE
Schoenberger
S P
SP
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D018398:Homeodomain Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein; D010047:Ovalbumin