Natural Killer Cells Regulate T-Cell Proliferation during Human Parainfluenza Virus Type 3 Infection

Abstract

Human parainfluenza virus type 3 (HPIV3) is a major respiratory pathogen in humans. Failure to induce immunological memory associated with HPIV3 infection has been attributed to inhibition of lymphocyte proliferation. We demonstrate that the inability of mixed lymphocytes to respond to virally infected antigenpresenting cells is due to an interleukin-2-dependent, nonapoptotic mechanism involving natural killer (NK) cells and their influence is exerted in a contact-dependent manner. These results suggest a novel regulatory mechanism for NK cells during HPIV3 infection, offering an explanation for viral persistence and poor memory responses.

Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

“…NK cells have been shown previously to play a role during influenza virus infection [63] and to regulate the functions of T lymphocytes during HPIV3 infection [64]. Here we showed NK cells play a role in viral clearance after recovery from immunosuppressive drug treatment.…”

Seoul Virus-Infected Rat Lung Endothelial Cells and Alveolar Macrophages Differ in Their Ability To Support Virus Replication and Induce Regulatory T Cell Phenotypes

“…Although using SEOV-specific T cells might be more physiologically relevant, isolation of SEOV-specific T cells from infected rats would not serve the purpose of the current study, which was to establish the cell type involved in the induction of Treg cells from a naïve CD4 ϩ T cell population. Allogeneic T cell cocultures have been used previously to systematically evaluate APC induction of T cell responses during virus infection (55,56,76). This mixed lymphocyte reaction or allogeneic T cell coculture system also has been used to study the induction of Treg cells by activated murine vascular endothelial cells (41) and human endothelial cells (72).…”

Utilization of mouse models to decipher natural killer cell biology and potential clinical applications

“…There have been studies using human cells that have shown similar lysis and regulation of T cells by NK cells in hepatitis B virus 27 and human parainfluenza virus type 3 28 that supported these findings in mice, but the clinical implications of this NK-mediated inhibition of T cells has not been demonstrated in humans. However, the clinical implications of these findings are still numerous in both viral and cancer disease states in terms of both trying to amplify the adaptive immune response to aid in eliminating the disease state and also to shut off the response, especially in influenza cases, where the adaptive immune cells lead to severe immunopathology that can be lethal.…”