Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections.
The rules for T-cell-mediated control of viruses that infect via the respiratory mucosae show both common themes and differences, depending on the nature of the pathogen. Virus-specific CD8+ cytotoxic T lymphocytes (CTLs) are the key effectors of virus clearance in mice infected with both negative strand RNA viruses (influenza and Sendai) and a DNA virus, the murine gamma-herpesvirus-68 (MHV-68). Recently completed experiments establish that these activated CD8+ T cells indeed operate primarily via contact-dependent lysis. Perforin-mediated cytotoxicity seems to be the preferred mode, though a Fas-based mechanism can apparently serve as an alternative mechanism. Immune CD4+ T cells functioning in the absence of the CD8+ subset cannot eliminate MHV-68 from lung epithelial cells, are somewhat less efficient than the CD8+ CTLs at clearing the RNA viruses, and are generally ineffectual in mice that lack B lymphocytes. Though cytokine secretion by CD4+ and CD8+ T cells in the virus-infected lung may promote both T-cell extravasation and macrophage activation, such processes are not alone sufficient to deal consistently with any of these infections. However, CD4+ T help is mandatory for an effective B-cell response, and can operate to promote the clonal expansion of virus-specific CD8+ T cells in the lymph nodes and spleen. Furthermore, a concurrent CD4+ T-cell response seems to be essential for maintaining continued CD8+ T-cell surveillance 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.
Doherty
P C
PC
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. peter.doherty@stjude.org
Topham
D J
DJ
Tripp
R A
RA
Cardin
R D
RD
Brooks
J W
JW
Stevenson
P G
PG
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D051379:Mice; D011024:Pneumonia, Viral / Q000276:immunology*; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000821:virology