Up-regulation of murine neonatal T helper cell responses by accessory cell factors.
We previously found that lymph node T cells from 4-day-old, naive neonatal mice show diminished Th1-like responses. Neonatal T cells produced low levels of IL-2 and proliferated poorly in response to soluble anti-CD3 stimulation. However, neonatal T cells resembled Th2 cells (or primed adult T cells) in that they produced large amounts of IL-4. Here, we have investigated the importance of accessory cell signals in the diminished Th1-like responses of neonatal T cells. Anti-CD28 mAb greatly augmented IL-2 production by neonatal T cells in response to plate-bound anti-CD3 Ab. In response to soluble anti-CD3 mAb plus accessory cells, exogenous accessory cell-derived cytokines were sufficient to restore neonatal responses to adult-like levels. In the presence of exogenous IL-6, IL-4 production by neonatal T cells was largely unchanged whereas IL-2 production was dramatically increased, reaching the high levels produced by adult T cells. In addition, the presence of exogenous IL-6 enhanced the proliferation of neonatal T cells to adult levels. IL-6 also had marked effects on the capacity of neonatal T cells to respond to secondary stimuli. In the absence of exogenous IL-6, neonatal T cells responded poorly to secondary stimulation. This lack of responsiveness was not overcome by the addition of IL-2 or by stimulation with phorbol ester and calcium ionophore. When IL-6 was present during the primary stimulation, neonatal T cells, like adult T cells, produced high levels of IL-4 and proliferated extensively in response to secondary stimuli. Thus, IL-6 was sufficient to restore both the primary and secondary responses of neonatal T cells to mature, adult-like levels. These results imply that neonatal T cells have a greater requirement for accessory cell signals than do adult T cells and may have important bearing in overcoming neonatal T cell immunodeficiencies in vivo.
Adkins
B
B
Department of Pathology, University of Miami Medical School, FL 33136.
Ghanei
A
A
Hamilton
K
K
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D005260:Female; D007156:Immunologic Memory / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D015850:Interleukin-6