Heterogeneous Cytokine Production by Acutely Stimulated Bronchoalveolar T Lymphocytes in Reovirus 1/Lang-Infected Mice

Abstract

While the in vitro properties of CD4+ and CD8+ cytokine-producing lymphocytes have been well studied, the in vivo cytokine production patterns and relative roles of CD4+ and CD8+ T lymphocytes during a primary in vivo immune response remain unclear. In this study, mice were inoculated intranasally with reovirus 1/L, and respiratory T lymphocyte populations were analyzed using multicolor flow cytometric analysis for the production of cytokine within and between classical type 1/type 2 patterns. Cytokine production observed in vivo following infection did not correlate with classical T cell cytokine expression patterns; instead, multiple types of lymphocyte populations that produced one of several possible cytokine combinations were present. Cytokine production by CD4+ lymphocytes appears in the early and middle stages of the immune response, while CD8+ lymphocytes produce more cytokine in the later stages. Early cytokine responses occurred predominantly in the whole lung and lung-associated lymph node populations. The complex patterns of cytokine expression seen in this study likely influence local cell-mediated immunity as well as the complex interaction of T cell subsets and the interaction of T cells with B cells which are necessary for the generation of cell-mediated and humoral immune responses required for effective broad-spectrum immunity.