Reduced activation and proliferation of human lymphocytes exposed to respiratory syncytial virus compared to cells exposed to influenza virus

Abstract

Both respiratory syncytial virus (RSV) and influenza A virus (IAV) may infect human peripheral blood mononuclear leukocytes (PBMC) during the immune response to viral challenge as the cells are recruited to the respiratory tract. The current studies demonstrated differences in PBMC responses to the two viruses very early after exposure, including reduced fos protein and CD69 expression and IL-2 production by RSV-exposed T lymphocytes. Exposure to RSV resulted in reduced lymphocyte proliferation despite evidence of a virus-specific T lymphocyte frequency equivalent to that for influenza virus. Reduced RSV-induced proliferation was not due to apoptosis, which was itself reduced relative to that of influenza virus-exposed T lymphocytes. The data indicate that differential immune responses to RSV and influenza virus are determined early after exposure of human PBMC and support the concept that the anamnestic immune response that might prevent clinically evident reinfection is attenuated very soon after exposure to RSV. Thus, candidate RSV vaccines should be expected to reduce but not prevent clinical illness upon subsequent infection by RSV. Furthermore, effective therapeutic agents for RSV are likely to be needed, especially for high-risk populations, even after vaccine development.

A comparison of RSV and influenza in vitro kinetic parameters reveals differences in infecting time

“…However, experimental infection of lymphocytes and macrophages with either virus has resulted in different IFN responses [ 109 , 110 ], and different interleukin responses [ 111 , 112 ]. Differences between the immune response to RSV and influenza in vivo have also been observed such as differences in which cytokines are secreted [ 10 ], in the interferon response [ 9 , 113 ], in the activation and proliferation of lymphocytes [ 114 ], and in the movement of dendritic cells and monocytes to the respiratory tract [ 11 ]. These different immune responses, particularly differences in the early innate immune response, could contribute to the observed differences in growth rate and time of peak.…”

Influenza Virus Infection of Human Lymphocytes Occurs in the Immune Cell Cluster of the Developing Antiviral Response

“…Our studies used whole PBMC populations rather than cloned virus-specific cells. Although the approach made it likely that only a small percentage of lymphocytes—the influenza virus-specific cells within the general population [ 55 , 56 , 57 ]—would cluster with monocytes-macrophages and become infected, the approach was considered to reflect more closely the likely in vivo situation with exposure to a challenging virus. Since we chose to use total normal PBMC preparations rather than cloned cells, we chose elutriation for lymphocyte purification because we needed a large number of highly purified lymphocytes for multiple autologous assays.…”

Diverse and Unexpected Roles of Human Monocytes/Macrophages in the Immune Response to Influenza Virus

“…Notably, however, aliquots of the IAV-exposed cells that responded poorly to mitogen stimulation were shown in concomitant assays to proliferate vigorously in response to IAV itself [16]. IAV-infected PBM actively supported IAV-specific lymphocyte activation and proliferation [16,18,19]. Furthermore, as noted above, the PBM actively responded to the IAV challenge in other ways, such as by the production of multiple cytokines, including interferon, interleukin (IL)-1, and tumor necrosis factor (TNF)α [10,11,20].…”