EFFECTOR CD4(-CELL MECHANISMS IN THE CONTROL OF RESPIRATORY VIRUS-INFECTIONS() AND CD8(+) T)

The rules for T-cell-mediated control of viruses that infect via the r espiratory mucosae show both common themes and differences, depending on the nature of the pathogen. Virus-specific CD8(+) cytotoxic T lymph ocytes (CTLs) are the key effecters of virus clearance in mice infecte d with both negative strand RNA viruses (influenza and Sendai) and a D NA virus, the murine gamma-herpesvirus-68 (MHV-68). Recently completed experiments establish that these activated CD8(+) T cells indeed oper ate primarily via contact-dependent lysis. Perforin-mediated cytotoxic ity seems to be the preferred mode, though a Fas-based mechanism can a pparently serve as an alternative mechanism. Immune CD4(+) T cells fun ctioning in the absence of the CD8(+) subset cannot eliminate MHV-68 f rom lung epithelial cells, are somewhat less efficient than the CD8(+) CTLs at clearing the RNA viruses, and are generally ineffectual in mi ce that lack B lymphocytes. Though cytokine secretion by CD4(+) and CD 8(+) T cells in the virus-infected lung may promote both T-cell extrav asation and macrophage activation, such processes are not alone suffic ient to deal consistently with any of these infections. However, CD4() T help is mandatory for an effective B-cell response, and can operat e to promote the clonal expansion of virus-specific CD8(+) T cells in the lymph nodes and spleen. Furthermore, a concurrent CD4(+) T-cell re sponse seems to be essential for maintaining continued CD8(+) T-cell s urveillance and effector capacity through the persistent, latent phase of MHV-68 infection in B cells. Thus, the evidence to date supports a very traditional view: CD8(+) T cells function mainly as killers and the CD4(+) T cells as helpers in these respiratory virus infections.