Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo

Abstract

Our data show that 1 x 107 to 1.5 x 107 lymphocytic choriomeningitis virus-specific, H-2-restricted cloned cytotoxic T lymphocytes (CTL) administered intravenously into acutely infected mice totally cleared virus from the spleens (104 to 105 PFU per spleen reduced to <50 PFU per spleen) by 24 h. This activity was genetically restricted in that cloned CTL could reduce titers of infectious virus in syngeneic C57BL/6 mice but not allogeneic BALB/c mice. Dose-response analysis indicated that at least 3 x 106 to 5 x 106 cloned CTL injected intravenously were needed to reduce significant amounts of infectious virus in the spleens. No infectious virus could be recovered from the spleens for at least 4 days after injection of cloned CTL. Hence, CTL play a major role in elimination of infectious virus from spleens during lymphocytic choriomeningitis virus infection. Our results also indicate that cloned CTL propagated in vitro for long periods of time can mediate a biologically relevant effect in vivo. These cells should be of considerable value in defining the precise manner in which CTL bring about control of viral infection, analyzing lymphocyte trafficking, and the potential use of cloned CTL in immunotherapy against viral disease.

Arenavirus genetic diversity and its biological implications

“…The virus in vivo in its natural host, the mouse, is non-cytolytic, and can cause either acute or persistent infections. When immunocompetent adult mice are injected with LCMV, they generate a robust immune response that results in virus clearance, which is mainly mediated by major histocompatibility complex (MHC) class-I restricted CD8 + antiviral cytotoxic T lymphocytes (CTL) (Byrne and Oldstone, 1984;Fung-Leung et al, 1991). By contrast, mice infected neonatally or in uterus with LCMV become persistently infected for life.…”

Mice Deficient in STAT1 but Not STAT2 or IRF9 Develop a Lethal CD4+T-Cell-Mediated Disease following Infection with Lymphocytic Choriomeningitis Virus

“…The development of LCM is dependent on CD8 ϩ effector T cells (12, 24, 29-31, 37, 79) but does not require CD4 ϩ T helper cells (24,58). Following peripheral infection, LCMV is cleared within 10 to 12 days postinfection, and virus elimination is mediated by virus-specific CD8 ϩ T cells (2,20,57,66,87,111), but not CD4 ϩ T cells or antiviral antibodies (2,66).…”

Immunosuppression and Virus Infection of Rodents

“…The recent development of methods for the cloning of T cells and the culture of T cell lines (88)(89)(90)(91)(92), has made it possible to study the effect of specific T cell subsets upon virus infection (93)(94)(95)(96). Again, although the data are still limited, it is clear that certain effector subsets, such as cytolytic T cells, are capable of clearing virus or (in the case of virus-induced immunopathology) of mediating disease.…”

“…Virus titers in suppressed and protected animals are high and, in fact, these mice become longterm virus carriers. Reconstitution experiments (98,99,102) show that antiviral antiserum will not reconstitute disease, while immune T cells (102), or cytolytic T cell clones (94,95), will induce acute disease when transferred into syngeneic recipients.…”