Control of CD4 effector fate: transforming growth factor beta 1 and interleukin 2 synergize to prevent apoptosis and promote effector expansion.

摘要: The signals that determine the size and duration of primary T cell immune response are not well defined. We studied CD4 cells at an important checkpoint in their development: when they have become effectors ready to rapidly mediate effector functions, both via direct interaction with antigen (Ag)-presenting cytokine production. determined effects specific Ag cytokines interleukin (IL) 2 transforming growth factor (TGF) beta 1 on helper type (Th2) apoptosis versus expansion. Th2-polarized were generated vitro from naive receptor transgenic mice, then restimulated or without peptide plus Ag-presenting cytokines. In absence added cytokines, cultured died after 4-7 d. Paradoxically, induced proliferation high levels synthesis accelerated death. IL-2 directly effectors, supported prolonged Ag-induced proliferation, partially blocked apoptosis. TGF-beta did effect influence secretion, but it also Together, synergized almost completely block apoptosis, resulting expansion leading accumulation a large pool effectors. When present, population increased 10(4)-10(5) fold over 20 d culture. synergy suggests interfere programmed death by distinct mechanisms. Since Th2 specialized help B develop into antibody-secreting plasma cells, these results suggest availability is key influencing fate thus antibody response.