Suppression of T Helper Function: An Immunoregulatory Effect of Rosette Inhibitory Factor in Hepatitis B Virus Infection

Abstract

The potential immunoregulatory effects of rosette inhibitory factor (RIF) were evaluated using lymphocyte subpopulations defined by monoclonal antibodies (OKT4, OKT8). Initial experiments indicated that RIF inhibits E–rosette formation by T cells that provide helper/inducer function (OKT4⁺). Subsequently, experiments were done to assess if RIF had an inhibitory effect on in vitro immunoglobulin and anti–HBs production. These studies used peripheral blood mononuclear cells from convalescent and hepatitis B–vaccinated donors. The results indicated that RIF–positive lowdensity lipoprotein, but not RIF–negative low–density lipoprotein, inhibits in vitro production of IgG and IgM by 60 to 70% and totally ablates anti–HBs synthesis. In order to determine if RIF directly affected the proliferative response of T4 lymphocytes, these cells were cultured in the presence of optimal mitogen concentrations and either RIF–positive or RIF–negative low–density lipoprotein. The experiments demonstrated that RIF–treated T4 cells are hyporesponsive to pokeweed mitogen and phytohemagglutinin when compared to T4 cells cultured in the absence of RIF. In contrast, B cell proliferation in response to soluble T helper factors was not affected by incubation with RIF. As the production of soluble helper factors by T4 cells was inhibited by exposure to RIF–positive but not RIF–negative low–density lipoprotein, we conclude that the suppressive effect of RIF on immunoglobulin and anti–HBs synthesis is due to inhibition of this specific helper T cell function.