Induction of self-reactive T cells after murine coronavirus infection

Abstract

We studied the mechanism of in vitro spontaneous lymphokine production by spleen cells from mice injected intraperitoneally with murine coronavirus strain JHM 1 month after infection, when infectious virus had already been cleared from the spleens. Removal of either CD4+ T cells or Ia+ antigen-presenting cells (APC) from the spleen cells abrogated interleukin-2 (IL-2) production. Addition of anti-CD4 or anti-Iad monoclonal antibodies to the culture suppressed IL-2 production. These results suggest that the response involved typical receptor-mediated activation of T cells. Surprisingly, reciprocal mixing experiments with a coculture of T cells from infected mice and APC from either infected or naive mice resulted in the production of IL-2. The absence of viral antigens in spleen cells 1 month after infection, as indicated by their inability to induce the proliferation of T-cell clones specific for the viral antigens, suggest that the T cells from mice 1 month after infection were not responding to the viral antigens. The inoculum components other than the virus did not induce this immune response. We also found that the frequency of self-reactive but not alloreactive IL-2-producing T cells in the spleens of infected mice was 3to 10-fold higher than that in naive mice. These findings suggest that an increased frequency of self-reactive T cells which secrete IL-2 occurs following murine coronavirus infection. This may have important implications in the development of autoimmunelike phenomena following murine coronavirus infection.

Annexin A2 on lung epithelial cell surface is recognized by severe acute respiratory syndrome-associated coronavirus spike domain 2 antibodies

“…Viral autoimmunity has been observed in various viral infections, such as human immunodeficiency virus (HIV), lymphocytic choriomeningitis virus (LCMV), hepatitis C virus (HCV), cytomegalovirus (CMV), and dengue virus (Barzilai et al, 2007;Christen et al, in press;Horwitz and Sarvetnick, 1999;Kim et al, 2005;Lin et al, 2006;Regner and Lambert, 2001;Rouse and Deshpande, 2002). Previous studies have demonstrated that mouse CoV infection can induce autoreactive T and B cell activation and the generation of autoantibodies (Hooks et al, 1993;Kyuwa et al, 1991;Mathieu et al, 2001). Autoimmunity may also be involved in SARS based on previous findings of anti-epithelial cell autoantibodies in SARS patients Lo et al, 2006;.…”

“…CoV-induced autoimmunity has been characterized previously. Infections of murine CoV such as mouse hepatitis virus induce autoreactive T cells, B cell polyclonal activation, and autoantibody production (Hooks et al, 1993;Kyuwa et al, 1991;Mathieu et al, 2001;Perlman and Dandekar, 2005). Furthermore, our previous studies showed the presence of autoantibodies in SARS patient sera that cross-reacted with the epithelial cell line A549 .…”

Coronavirus infects and causes demyelination in primate central nervous system

“…There have been no subsequent reports supporting this link between coronaviruses and human demyelination . However, data showing that these viruses produce demyelination (Bailey et al, 1949 ;Pappenheimer, 1958 ;Weiner, 1973 ;Herndon et al, 1975 ;Lucas et al, 1977 ;Nagashima et al, 1978 ;Sorensen at al ., 1980 ;Lavi et al, 1984) and stimulate T-cell mediated autoimmune reactions against CNS antigens in rodents (Stohlman and Weiner, 1981 ;Watanabe et al, 1983 ;Kyuwa et al, 1991) suggest that the question concerning the link between coronaviruses and neurologic disease in humans is open .…”

Transcriptome profile within the mouse central nervous system and activation of myelin-reactive T cells following murine coronavirus infection

“…It has previously been demonstrated that MHV-JHM infection of mouse can lead to the activation of self-reactive T cells, which produce IL-2 in the presence of antigenpresenting cells and in the absence of viral antigen (Kyuwa et al, 1991). Furthermore, it was also reported several years ago that rats infected with MHV-JHM showed T-cell proliferation upon stimulation with myelin basic protein (MBP), and adoptive transfer of these cells to naive rats led to an experimental allergic encephalomyelitis (EAE)-like disease.…”

“…Moreover, infection of mice with the HCoV murine counterpart, murine hepatitis virus (MHV), provides an excellent experimental animal model for MS studies (Lane and Buchmeier, 1997). Indeed, this model has already been used to demonstrate the activation of autoreactive T cells in mice following infection (Kyuwa et al, 1991) and the activation of myelin-specific T cells in infected rats (Watanabe et al, 1983). In addition, naive animals that received T cells from infected rats restimulated by MBP, developed an EAE-like lesions (Watanabe et al, 1983).…”