Cg. Sagerstrom et al., ACTIVATION AND DIFFERENTIATION REQUIREMENTS OF PRIMARY T-CELLS IN-VITRO, Proceedings of the National Academy of Sciences of the United Statesof America, 90(19), 1993, pp. 8987-8991
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 alphabeta transgenic anima
ls and peptide-major histocompatibility (MHC) complexes coated on plat
es. Whereas previously stimulated T cells require only peptide-MHC com
plexes to produce interleukin 2 (IL-2), naive cells require at least o
ne additional signal, which can be provided by either an anti-CD28 ant
ibody or the protein kinase C stimulant phorbol 12-myristate 13-acetat
e. In contrast, the anti-CD28 antibody augments IL-2 production by pri
med T cells but is not required, and phorbol 12-myristate 13-acetate h
as no discernable effect. Thus we find that naive T cells have signifi
cantly more stringent requirements for IL-2 production than primed cel
ls and that this fits well with previous observations in other in vitr
o systems as well as in vivo models of autoimmunity. We also find that
peptide-MHC complex stimulation of naive T cells, together with exoge
nous IL-2, is sufficient to convert these cells to primed T cells in v
itro in 2 days, as assayed both by surface marker analysis and stimula
tion requirements. Taken together with the above results, this suggest
s 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 autocri
ne fashion to allow them to proliferate and differentiate.