A gamma-herpesvirus sneaks through a CD8(+) T cell response primed to a lytic-phase epitope.
To determine whether established CD8(+) T cell memory to an epitope prominent during the replicative phase of a gamma-herpesvirus infection protects against subsequent challenge, mice were primed with a recombinant vaccinia virus expressing the p56 peptide and then boosted by intranasal exposure to an influenza A virus incorporating p56 in the neuraminidase protein. Clonally expanded populations of functional, p56-specific CD8(+) T cells were present at high frequency in both the lung and the lymphoid tissue 1 month later, immediately before respiratory challenge with gammaHV-68. This prime-and-boost regime led to a massive reduction of productive gammaHV-68 infection in the respiratory tract and, initially, to much lower levels of latency in both the regional lymph nodes and the spleen. The CD8(+) T cell response to another epitope (p79) was diminished, there was less evidence of B cell activation, and the onset of the CD4(+) T cell-dependent splenomegaly was delayed. Within 3-4 weeks of the gammaHV-68 challenge, however, the extent of latent infection in the lymph nodes and spleen was equivalent, and both groups developed the prominent infectious mononucleosis-like syndrome that is characteristic of this infection. The reverse protocol (influenza then vaccinia) seemed to be slightly less effective. Even though immune CD8(+) T cells may be present at the time and site of virus challenge, establishing a high level of CD8(+) T cell memory to lytic-phase epitopes alone does not protect against the longer-term consequences of this gammaHV infection.
Stevenson
P G
PG
Department of Immunology, St. Jude Children's Research Hospital, Memphis TN 38105, USA.
Belz
G T
GT
Castrucci
M R
MR
Altman
J D
JD
Doherty
P C
PC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D018142:Gammaherpesvirinae / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013163:Splenomegaly / Q000276:immunology; D013997:Time Factors; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D007371:Interferon-gamma