Rotavirus induces proliferative response and augments non-specific cytotoxic activity of lymphocytes in humans

Abstract

In vitro cell-mediated immune responses to rotavirus in humans were studied. Peripheral blood mononuclear cells (PBMC) of healthy adults proliferated in response to stimulation with the infectious and u.v.-inactivated Wa strain of human rotavirus, showing a maximum response on day 7 of culture; however, cord blood lymphocytes failed to respond to rotavirus. A cross-reactive proliferative response of PBMC detected by stimulation with the NCDV strain of bovine rotavirus suggests the existence of epitopes common to both human and bovine rotaviruses, which are recognized by human T lymphocytes. The phenotype of the majority of activated lymphocytes was CD3+4+8-, indicating that the cells mainly activated were helper T cells. Culture supernatants of PBMC stimulated with rotavirus contained interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). In addition, PBMC stimulated with rotavirus demonstrated significantly enhanced cytotoxic activity against natural killer (NK) sensitive K562 cells as well as an NK-resistant Epstein-Barr virus-immortalized lymphoblastoid cell line (LCL). Treatment of PBMC with anti-CD16 or NKH1A monoclonal antibody, both of which react with most NK cells and lymphokine-activated killer cells and complement markedly reduced the cytotoxic activity against K562 and LCL. These results suggest that stimulation of human PBMC with rotavirus results in the production of lymphokines, such as IL-2 and IFN-gamma, by rotavirus-reactive helper T cells and that these lymphokines augment NK activity and generate other forms of non-specific cytotoxic human lymphocyte activity. These cell-mediated immune responses observed in the present in vitro study might play an important role in protection and recovery from rotavirus infection.