We have observed the disappearance of rosette inhibitory factor (RIF) from the serum of 19 patients with acute hepatitis B virus infection. This occurred at a time coinciding with the detection of anti-HBs. In addition, levels of RIF activity were significantly greater (p < 0.001) in 35 HBsAg carriers who lacked anti-HBs when compared to 15 carriers who regularly demonstrated this antibody. In all instances, RIF effect was partial affecting some, but not all, T-lymphocytes from forming erythrocyte rosettes.

To define if RIF exhibits an effect on specific T-lymphocyte subpopulations, lymphocytes from healthy donors were separated into TM (helper), TG (suppressor), and To (null) subpopulations by an immunoglobulin-ox-cell rosette depletion method. The effect of RIF on erythrocyte rosette formation and Fc-receptor expression in these subpopulations was assessed. TG-lymphocytes were found to be refractory to RIF-mediated suppression of erythrocyte rosette formation while TM-lymphocytes demonstrated an enhanced sensitivity to RIF. Incubation of TG- and To-lymphocytes, potential TM-precursor cells, with RIF resulted in a decreased expression of new IgM-Fc receptors.

In order to determine if any functional significance could be derived from these findings, the effect of RIF on in vitro immunoglobulin secretion was tested. Using pokeweed mitogen-stimulated mononuclear cell cultures, purified RIF-low density lipoprotein was shown to suppress IgM, IgG, and IgA secretion by 75.3, 74.3, and 59.3%, respectively.

These data are consistent with the hypothesis that RIF is a potential immunoregulatory protein which could contribute to the lack of anti-HBs noted during the acute phase of hepatitis B and in the majority of HBsAg carriers.