Divergence between cytotoxic effector function and tumor necrosis factor alpha production for inflammatory CD4+ T cells from mice with Sendai virus pneumonia.

Sendai virus pneumonia in beta 2-microglobulin-deficient [beta 2-m(-/-)] mice lacking CD8+ T cells is characterized by the development of CD4+ cytotoxic T lymphocytes that can be recovered directly from the respiratory tract. These CD4+ cytotoxic T lymphocytes are not found in beta 2-m (+/+) mice, though inflammatory CD4+ T cells from both beta 2-m (-/-) and beta 2-m (+/+) mice produce substantial amounts of tumor necrosis factor alpha. Blocking experiments with a monoclonal antibody that also inhibits tumor necrosis factor beta show that the secreted forms of these two cytokines are not responsible for virus-specific killing of class II major histocompatibility complex-compatible targets. Comparison of electron micrographs indicates that the CD4+ effectors from the beta 2-m (-/-) mice are potent inducers of apoptosis, while this is not the case for the beta 2-m (+/+) CD4+ set. These experiments further define the functional status of virus-specific CD4+ T cells responding in vivo in the presence or absence of CD8+ effectors.