Bacterial lipopolysaccharide (endotoxin) interferes with the induction of tolerance and primes thymus-derived lymphocytes

Abstract

The injection of deaggregated human gamma-globulin (DHGG) into mice results in the establishment of specific immunologic unresponsiveness in T and B lymphocytes. However, the additional injection of bacterial lipopolysaccharide (LPS) 3 hr later converts the tolerogenic DHGG into an immunogen for both helper T and B cells. This generation of immunocompetence to HGG during interference with tolerance induction by LPS is demonstrated by both a primary plaque-forming cell response to DHGG + LPS and a secondary antibody response to a subsequent antigenic challenge. The secondary response to antigen stimulation in the B cells is, however, T cell dependent. Interference with tolerance induction in antigen-specific helper T cells can be demonstrated by challenge with the DNP-HGG hapten-carrier conjugate or by adoptive cell transfer with primed B cells and subsequent challenge with immunogenic HGG. Furthermore, helper T cells in the spleen and thymus become primed by DHGG + LPS as evidenced by their cooperation with primed B cells in the adoptive transfer assay. In addition to its interference with tolerance induction, LPS injected with either tolerogenic or immunogenic HGG also facilitates priming of helper T cells for the response to DNP-HGG. These data indicate that exposure of antigen-specific helper T and B cells to antigen alone results in the induction of tolerance, whereas induction of immunocompetence in these cells requires at least 2 signals, 1 provided by interaction with antigen and a 2nd delivered by a nonspecific stimulus similar to that provided by LPS in the present experiments.