title: Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1beta or interferon-gamma.
abstract: Transgenic (Tg) mice expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter exhibit tolerance to HEL by both their T- and B-cell compartments. Here, we show that double-Tg mice, coexpressing HEL with either interleukin-1beta or interferon (IFN)-gamma, demonstrated unresponsiveness to HEL by their T-cell compartment, but most of them developed antibodies against HEL following a challenge with the antigen. The abrogation of humoral tolerance was more pronounced in the HEL/IL-1 double-Tg mice than in the HEL/IFN-gamma mice. Unlike their controls, double-Tg mice exhibited remarkable levels of variability in their antibody levels. The skewed abrogation of tolerance in the double-Tg mice is proposed to be due to the cytokines' capacity to rescue from clonal deletion small numbers of T cells, which provide help to antibody producing B cells. This notion is supported by the finding that adoptive transfer of small numbers of Th1 or Th2 cells into HEL-Tg mice made possible antibody production similar to that seen in the double-Tg mice.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Fukushima
authors.forename: B P
authors.initials: BP
authors.lastname: Vistica
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Hung
authors.forename: E F
authors.initials: EF
authors.lastname: Wawrousek
authors.forename: C E
authors.initials: CE
authors.lastname: Egwuagu
authors.forename: R S
authors.initials: RS
authors.lastname: Lee
authors.forename: S M
authors.initials: SM
authors.lastname: Whitcup
authors.forename: I
authors.initials: I
authors.lastname: Gery
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D001324:Autoantigens; D007375:Interleukin-1; D007371:Interferon-gamma; D009113:Muramidase