Rosette Inhibitory Factor: T-Lymphocyte Subpopulation Specificity and Potential Immunoregulatory Role in Hepatitis B Virus Infection

Abstract

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-lyrnphocytes demonstrated an enhanced sensitivity to RIF. Incubation of Tc-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 uitro 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.Rosette inhibitory factor (RIF) is a unique serum, lowdensity lipoprotein (LDL) which is detectable during infection with hepatitis A, B, and non-A, non-B viruses (1-3). This factor inhibits healthy T-lymphocytes from forming sheep erythrocyte rosettes (E rosette), a marker for the functional integrity of T-cells. It has been suggested that RIF may behave as an immunoregulatory molecule (4) but direct evidence for this assumption is lacking. Studies from our laboratory support the sugges-

Immune Responses and Liver Disease, Perhaps. But What About Target Organ Defenses?

“…How well it will age only time will tell. Following an earlier delineation of an immunoregulatory serum factor (SIF) in acute and chronic viral hepatitis by Berg et al (12) and progress in further characterizing the role of the viral induced rosette inhibitory factor as a modulator of helper cell differentiation and determinant of the anti-HbsAg response by Perillo and colleagues (8,9), a series of new studies has emerged. Following the biochemical characterization of liver-derived inhibitory protein (LIP) by Grol and Schumacher (13), perhaps the same as LEx (ll), a new immunosuppressive serum factor (SIF) is described in this issue by Brattig et al (1).…”