Passive immunotherapy for retroviral disease: influence of major histocompatibility complex type and T-cell responsiveness.

Abstract

Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibodymediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4+ and CD8+ T lymphocytes. Thus, cellmediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed.

Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection

“…3, 4A). However, the total number of CD4 + CD25 + T cells was two-to threefold higher in persistently infected mice due to an enlarged spleen size in chronic infection [8]. During acute infection, a temporal correlation between expansion of GITR or CD103 expressing CD4 + T cells and CD8 + T cell suppression was also evident.…”

“…In contrast, resistant strains, like (B10 Â AB.Y)F1 or C57BL/6 mice, develop potent immune responses that allow recovery from acute infection and prevent onset of leukemia [6]. CD8 + T cells are absolutely critical for this recovery, as animals lacking CD8 + T cells can no longer control virus replication and develop severe disease [7][8][9]. These CD8 + T cells utilize the cytotoxic molecules perforin, granzyme A, and granzyme B to kill FV-infected cells during the first weeks of infection [10].…”

Class Switch Recombination and Somatic Hypermutation of Virus-Neutralizing Antibodies Are Not Essential for Control of Friend Retrovirus Infection

“…Each data point shows the mean Ϯ SEM calculated with data from five to six mice per group. demonstrated the requirement of host T cells for passive immunotherapy with FV-neutralizing monoclonal IgG (16). Similarly, no protection was observed when the recipients were not previously immunized.…”

Essential role for virus-neutralizing antibodies in sterilizing immunity against Friend retrovirus infection

“…To determine whether virus-neutralizing antibodies could substitute for the absence of B cells in B6.UMT mice, passive transfer experiments were performed using virus-neutralizing mAb 48 specific for the FV Env protein (45,49). Passive transfer of mAb 48 has been shown to reduce viremia levels in vivo without inducing antibody-dependent cellular cytotoxicity in infected cells (50).…”