Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8+ T-cell priming and viral control

Abstract

Clinically used human vaccination aims to induce specific antibodies that can guarantee longterm protection against a pathogen. The reasons that other immune components often fail to induce protective immunity are still debated. Recently we found that enforced viral replication in secondary lymphoid organs is essential for immune activation. In this study we used the lymphocytic choriomeningitis virus (LCMV) to determine whether enforced virus replication occurs in the presence of virus-specific antibodies or virus-specific CD8 + T cells. We found that after systemic recall infection with LCMV-WE the presence of virus-specific antibodies allowed intracellular replication of virus in the marginal zone of spleen. In contrast, specific antibodies limited viral replication in liver, lung, and kidney. Upon recall infection with the persistent virus strain LCMV-Docile, viral replication in spleen was essential for the priming of CD8 + T cells and for viral control. In contrast to specific antibodies, memory CD8 + T cells inhibited viral replication in marginal zone but failed to protect mice from persistent viral infection. We conclude that virus-specific antibodies limit viral infection in peripheral organs but still allow replication of LCMV in the marginal zone, a mechanism that allows immune boosting during recall infection and thereby guarantees control of persistent virus.Memory formation after antigen challenge is one of the most important hallmarks of the adaptive immune system 1 ; it protects the host from exposure to the original or a slightly modified pathogen 1 . Because of this known memory formation, vaccination with attenuated pathogens has been an important tool for preventing outbreaks of severe pathogen-mediated diseases. In the Western world, the World Health Organization recommends approximately 16 vaccinations 2 , 10 of which are antiviral.Although virus-specific CD8 + T cells are known to contribute to the control of viral infections, all recommended vaccinations are aimed at inducing antibodies against a pathogen 3-7 . For example, newly designed vaccines against HIV are intended to specifically activate HIV-specific CD8 + T cells 8 . However, to date, CD8 + T cell-mediated vaccines have failed to protect the host from persistent infection 9 . Therefore, the role of vaccine-induced virus-specific CD8 + T cells in long-term protection is still being debated [10][11][12] . To know in more

Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

“…Notably, anti-LCMV antibodies limited viral replication in peripheral organs, but allowed replication of the virus in the marginal zone of the spleen, promoting CD8 + T-cell priming. 66 Interestingly, anti-LCMV antibodies were also reported to be essential for long-term maintenance of the memory CTL response in infected mice. 67,68 These observations, together with the in vitro studies described above, demonstrate that virus-specific antibodies can promote the acquisition, processing and presentation of antigens that are subsequently instrumental for priming T-cell responses and programming functional CD8 + memory in an Fc-dependent manner.…”

Mechanisms of lymphatic system-specific viral replication and its potential role in autoimmune disease

“…This boosting results in rapid control of the virus, even in the case of infection with the highly persistent LCMV strain Docile. In this situation, virus control is dependent on CD169 + macrophages and on the priming of new virus-specific CD8 + T cells [55].…”