Heterogeneous cytokine production by acutely stimulated bronchoalveolar T lymphocytes in reovirus 1/lang-infected mice

While the in vitro properties of CD4(+) and CD8(+) cytokine-producing lymph ocytes 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 intran asally with reovirus 1/L, and respiratory T lymphocyte populations were ana lyzed using multicolor flow cytometric analysis for the production of cytok ine within and between classical type 1/type 2 patterns. Cytokine productio n observed in vivo following infection did not correlate with classical T c ell cytokine expression patterns; instead, multiple types of lymphocyte pop ulations that produced one of several possible cytokine combinations were p resent. 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 predominan tly in the whole lung and lung-associated lymph node populations. The compl ex patterns of cytokine expression seen in this study likely influence loca l cell-mediated immunity as well as the complex interaction of T cell subse ts and the interaction of T cells with B cells which are necessary for the generation of cell-mediated and humoral immune responses required for effec tive broad-spectrum immunity. (C) 1999 Academic Press.