Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppressionin vitro

Abstract

A marked suppression of immune function has long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. As a hallmark of measles virus (MV)-induced immunosuppression, peripheral blood lymphocytes (PBLs) isolated from patients exhibit a significantly reduced capacity to proliferate in response to mitogens, allogens, or recall antigens. In an in vitro system we show that proliferation of naive PBLs [responder cells (RCs)] in response to a variety of stimuli was significantly impaired after cocultivation with MV-infected, UV-irradiated autologous PBLs [presenter cells (PCs)]. We further observed that a 50% reduction in proliferation of RCs could still be observed when the ratio of PC to RC was 1:100. The effect was completely abolished after physical separation of the two populations, which suggests that soluble factors were not involved. Proliferative inhibition of the RCs was observed after short cocultivation with MV-infected cells, which indicates that surface contact between one or more viral proteins and the RC population was required. We identified that the complex of both MV glycoproteins, F and H, is critically involved in triggering MV-induced suppression of mitogen-dependent proliferation, since the effect was not observed (i) using a recombinant MV in which F and H were replaced with vesicular stomatitis virus G or (ii) when either of these proteins was expressed alone. Coexpression of F and H, however, lead to a significant proliferative inhibition in the RC population. Our data indicate that a small number of MV-infected PBLs can induce a general nonresponsiveness in uninfected PBLs by surface contact, which may, in turn, account for the general suppression of immune responses observed in patients with acute measles.

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

“…MV infection has been shown to affect DC function; MVinfected DCs are unable to stimulate a mixed lymphocyte reaction and can induce lymphocyte unresponsiveness through expression of MV glycoproteins [40,41]. Therefore, it is possible that MV interferes with the cross-presentation antigen-processing pathway of primary LCs.…”

“…Previously, immature LCs were found susceptible for MV [26], but they might have been more activated as others showed that mechanical stress facilitates LC activation and MV infection [25]. Therefore, differences in activation status of LCs determine susceptibility to MV.MV infection has been shown to affect DC function; MVinfected DCs are unable to stimulate a mixed lymphocyte reaction and can induce lymphocyte unresponsiveness through expression of MV glycoproteins [40,41]. Therefore, it is possible that MV interferes with the cross-presentation antigen-processing pathway of primary LCs.…”

Lymphotropism and host responses during acute wild-type canine distemper virus infections in a highly susceptible natural host

“…Thus, accumulating evidence strongly links immunosuppression and lymphopenia not only to direct effects following infection and subsequent destruction of signalling lymphocytic activating molecule (SLAM)-positive immune cells and precursor cells in the acute phase of the infections, but also to indirect effects modulating the host innate and adaptive immune systems (Cruz et al, 2006;Devaux et al, 2008;Heaney et al, 2005;Karp et al, 1996;Schlender et al, 1996;Tatsuo et al, 2001;von Messling et al, 2006). The relative impact on virulence of the different mechanisms modulating the immune system in vivo is, however, not yet clarified.…”

A recombinant measles virus expressing biologically active human interleukin-12.

“…Peripheral blood lymphocytes (PBLs) isolated from measles patients show a reduced proliferation capacity in response to polyclonal stimulation (Hirsch et al, 1984 ;Whittle et al, 1978) possibly due to a cell cycle arrest in the end of the G1 phase (McChesney et al, 1987(McChesney et al, , 1988. Even uninfected PBLs were shown to exhibit decreased proliferation in presence of cells that express measles glycoproteins (Niewiesk et al, 1997 ;Schlender et al, 1996). In addition, MV infection also influences the maturation, survival and functioning of dendritic cells (DCs) (Fugier-Vivier et al, 1997 ;Grosjean et al, 1997 ;Schnorr et al, 1997).…”