Respiratory Mucosal Immunization with Reovirus Serotype 1/L Stimulates Virus-Specific Humoral and Cellular Immune Responses, Including Double-Positive (CD4 + /CD8 + ) T Cells

Abstract

ABSTRACT Respiratory virus infections are a serious health challenge. A number of models that examine the nature of the respiratory immune response to particular pathogens exist. However, many pathogens that stimulate specific immunity in the lung are frequently not effective immunogens at other mucosal sites. A pathogen that is an effective respiratory as well as gastrointestinal immunogen would allow studies of the interaction between the mucosal sites. Reovirus (respiratory enteric orphan virus) serotype 1 is known to be an effective gut mucosal immunogen and provides a potential model for the relationship between the respiratory and the gut mucosal immune systems. In this study, we demonstrate that intratracheal immunization with reovirus 1/Lang (1/L) in C3H mice resulted in high titers of virus in the respiratory tract-associated lymphoid tissue (RALT). High levels of reovirus-specific immunoglobulin A were determined in the RALT fragment cultures. The major responding components of the bronchus-associated lymphoid tissue were the CD8 + T lymphocytes. Cells from draining lymph nodes also exhibited lysis of reovirus-infected target cells after an in vitro culture. The present study also describes the distribution of transiently present CD4 + /CD8 + double-positive (DP) T cells in the mediastinal and tracheobronchial lymph nodes of RALT. CD4 + /CD8 + DP lymphocytes were able to proliferate in response to stimulation with viral antigen in culture. Furthermore, these cells exhibited lysis of reovirus-infected target cells after in vitro culture. These results establish reovirus 1/L as a viable model for future investigation of the mucosal immune response in the RALT and its relationship to the common mucosal immune system.