Roland Kurrle

Inhibition of allergen-induced IgE and IgG1 production by soluble IL-4 receptor

In this study, the effect of soluble IL-4 receptors (sIL-4R) on murine allergen-induced IgE and IgG1 production was examined. Lymphocytes from mice sensitized to the allergens ragweed (RW) or ovalbumin (OVA) in vivo were restimulated in vitro with the sensitizing allergen in the presence of either a soluble murine sIL-4R, a dimeric sIL-4R Ig fusion protein (sIL-4R/Fc), or anti-IL-4 antibody in 14-day cultures. Both monomeric and dimeric sIL-4R inhibited polyclonal IgE (approximately 70%) and IgG1 (approximately 35%) production in a dose-dependent fashion, similar to that observed in the presence of the anti-IL-4 antibody. Allergen-specific IgE and IgG1 were inhibited to a greater degree. Addition of sIL-4R was most effective when present in the culture during the first 3 days and added not later than day 6. In kinetic experiments, we distinguished ongoing IgE production from precommitted B cells versus newly induced IgE synthesis and found that newly induced IgE production was the major target of the sIL-4Rs. These data demonstrate the efficacy of sIL-4R in inhibiting the early stages of the IgE B-cell maturation pathway and indicate the potential of sIL-4R for the inhibition of IgE production in vivo.

Anti H-2Dd alloreactivity mediated by herpes-simplex-virus specific cytotoxic H-2k T lymphocytes is associated with H-2Dk

Herpes-simplex-virus (HSV) specific, H-2k-restricted, immune cytotoxic T lymphocytes also lyse noninfected H-2d target cells. Genetic mapping studies revealed that HSV-specific Dk-restricted CTL cross-react with allogeneic targets expressing Dd alloantigens. Cold target inhibition experiments indicate that only a minority of HSV-specific CTL mediate cross-reactive cytolysis. The data give an example of where the phenomenon of H-2-restricted versus nonrestricted responsiveness is not due to distinct subsets of T cells but solely depends on the antigenic determinants recognized.