Virus-specific CD8(+) T cell numbers are maintained during gamma-herpesvirus reactivation in CD4-deficient mice.
The murine gamma-herpesvirus 68 replicates in epithelial sites after intranasal challenge, then persists in various cell types, including B lymphocytes. Mice that lack CD4(+) T cells (I-Ab-/-) control the acute infection, but suffer an ultimately lethal recrudescence of lytic viral replication in the respiratory tract. The consequences of CD4(+) T cell deficiency for the generation and maintenance of murine gamma-herpesvirus 68-specific CD8(+) set now have been analyzed by direct staining with viral peptides bound to major histocompatibility complex class I tetramers and by a spectrum of functional assays. Both acutely and during viral reactivation, the CD8(+) T cell responses in the I-Ab-/- group were no less substantial than in the I-Ab+/+ controls. Indeed, virus-specific CD8(+) T cell numbers were increased in the lymphoid tissue of clinically compromised I-Ab-/- mice, although relatively few of the potential cytotoxic T lymphocyte effectors were recruited back to the site of pathology in the lung. Thus the viral reactivation that occurs in the absence of CD4(+) T cells was not associated with any exhaustion of the virus-specific cytotoxic T lymphocyte response. It seems that CD8(+) T cells alone are insufficient to maintain long-term control of this persistent gamma-herpesvirus.
Stevenson
P G
PG
The Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Belz
G T
GT
Altman
J D
JD
Doherty
P C
PC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D005260:Female; D018142:Gammaherpesvirinae / Q000254:growth & development* / Q000276:immunology*; D005802:Genes, MHC Class II; D006566:Herpesviridae Infections / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D013154:Spleen / Q000276:immunology; D014775:Virus Activation
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II