UP-REGULATION OF MURINE NEONATAL T-HELPER CELL RESPONSES BY ACCESSORYCELL FACTORS

We previously found that lymph node T cells from 4-day-old, naive neon atal mice show diminished Th1-like responses. Neonatal T cells produce d low levels of IL-2 and proliferated poorly in response to soluble an ti-CD3 stimulation. However, neonatal T cells resembled Th2 cells (or primed adult T cells) in that they produced large amounts of IL-4. Her e, we have investigated the importance of accessory cell signals in th e diminished Th1-like responses of neonatal T cells. Anti-CD28 mAb gre atly augmented IL-2 production by neonatal T cells in response to plat e-bound anti-CD3 Ab. In response to soluble anti-CD3 mAb plus accessor y cells, exogenous accessory cell-derived cytokines were sufficient to restore neonatal responses to adult-like levels. In the presence of e xogenous IL-6, IL-4 production by neonatal T cells was largely unchang ed whereas IL-2 production was dramatically increased, reaching the hi gh levels produced by adult T cells. In addition, the presence of exog enous IL-6 enhanced the proliferation of neonatal T cells to adult lev els. IL-6 also had marked effects on the capacity oi neonatal T cells to respond to secondary stimuli. In the absence of exogenous IL-6, neo natal T cells responded poorly to secondary stimulation. This lack of responsiveness was not overcome by the addition of IL-2 or by stimulat ion with phorbol ester and calcium ionophore. When IL-6 was present du ring the primary stimulation, neonatal T cells, like adult T cells, pr oduced high levels of IL-4 and proliferated extensively in response to secondary stimuli. Thus, IL-6 was sufficient to restore both the prim ary and secondary responses of neonatal T cells to mature, adult-like levels. These results imply that neonatal T cells have a greater requi rement for accessory cell signals than do adult T cells and may have i mportant bearing in overcoming neonatal T cell immunodeficiencies in v ivo.