Activation and differentiation requirements of primary T cells in vitro.
The progression of T cells from a quiescent or resting state to fully activated, proliferating cells is a crucial step in the initiation of an immune response. We have developed an in vitro system to study the requirements for triggering or hindering this pathway by using naive T cells derived from T-cell antigen receptor alpha beta transgenic animals and peptide-major histocompatibility (MHC) complexes coated on plates. Whereas previously stimulated T cells require only peptide-MHC complexes to produce interleukin 2 (IL-2), naive cells require at least one additional signal, which can be provided by either an anti-CD28 antibody or the protein kinase C stimulant phorbol 12-myristate 13-acetate. In contrast, the anti-CD28 antibody augments IL-2 production by primed T cells but is not required, and phorbol 12-myristate 13-acetate has no discernable effect. Thus we find that native T cells have significantly more stringent requirements for IL-2 production than primed cells and that this fits well with previous observations in other in vitro systems as well as in vivo models of autoimmunity. We also find that peptide-MHC complex stimulation of naive T cells, together with exogenous IL-2, is sufficient to convert these cells to primed T cells in vitro in 2 days, as assayed both by surface marker analysis and stimulation requirements. Taken together with the above results, this suggests that the activation of primary T cells requires at least two signals and that IL-2 produced by naive T cells in vivo may act in an autocrine fashion to allow them to proliferate and differentiate.
Sagerström
C G
CG
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5428.
Kerr
E M
EM
Allison
J P
JP
Davis
M M
MM
D000818:Animals; D002454:Cell Differentiation; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006649:Histocompatibility Antigens; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013755:Tetradecanoylphorbol Acetate