Requirement for CD4+ T cells in V beta 4+CD8+ T cell activation associated with latent murine gammaherpesvirus infection.
A CD8+ T cell lymphocytosis in the peripheral blood is associated with the establishment of latency following intranasal infection with murine gammaherpesvirus-68. Remarkably, a large percentage of the activated CD8+ T cells of mice expressing different MHC haplotypes express V beta 4+ TCR. Identification of the ligand driving the V beta 4+CD8+ T cell activation remains elusive, but there is a general correlation between V beta 4+CD8+ T cell stimulatory activity and establishment of latency in the spleen. In the current study, the role of CD4+ T cells in the V beta 4+CD8+ T cell expansion has been addressed. The results show that CD4+ T cells are essential for expansion of the V beta 4+CD8+ subset, but not other V beta subsets, in the peripheral blood. CD4+ T cells are required relatively late in the antiviral response, between 7 and 11 days after infection, and mediate their effect independently of IFN-gamma. Assessment of V beta 4+CD8+ T cell stimulatory activity using murine gammaherpesvirus-68-specific T cell hybridomas generated from latently infected mice supports the idea that CD4+ T cells control levels of the stimulatory ligand that drives the V beta 4+CD8+ T cells. As V beta 4+CD8+ T cell expansion also correlates with levels of activated B cells, these data raise the possibility that CD4+ T cell-mediated B cell activation is required for optimal expression of the stimulatory ligand. In addition, in cases of low ligand expression, there may also be a direct role for CD4+ T cell-mediated help for V beta 4+CD8+ T cells.
Flaño
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E
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Woodland
D L
DL
Blackman
M A
MA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D016827:CD8 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D018142:Gammaherpesvirinae / Q000276:immunology / Q000502:physiology*; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017735:Virus Latency / Q000276:immunology*
D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma