Changing patterns of dominance in the CD8+ T cell response during acute and persistent murine γ-herpesvirus infection

Abstract

The murine +-herpesvirus MHV-68 causes an acute, transient pneumonitis, followed by an infectious mononucleosis (IM)-like illness with splenomegaly, widespread latent infection of B lymphocytes and an expansion of V g 4 + CD8 + T cells. CD8 + T cells specific for an H-2D b-restricted epitope were prominent during the acute respiratory infection, but their prevalence declined rapidly during the mononucleosis. In contrast, CD8 + T cells specific for an H-2K b-restricted epitope, apparently expressed by virus-infected B lymphocytes, were most numerous during the mononucleosis illness and were maintained at relatively high frequencies thereafter. The prevalence of all peptide-specific CD8 + T cells decreased during the expansion of the V g 4 + CD8 + population, which did not recognize any peptide epitopes identified and was apparent also in an MHC class I-deficient environment. The CD8 + T cell population recognizing productively infected epithelial cells thus differed substantially from that responding during the IM illness.

Postexposure vaccination massively increases the prevalence of γ-herpesvirus-specific CD8+T cells but confers minimal survival advantage on CD4-deficient mice

“…Each value is the mean Ϯ SD for the percent in the CD8 ϩ set in three separate experiments. The results for those that were given vacc-LCMV b are equivalent to the virus-specific CD8 ϩ T cell frequencies found normally in ␥HV-68-infected I-A bϩ/ϩ mice (12,14). *The CD8 ϩ T cells in the PEL (and spleen) samples recovered from mice that had never been exposed to ␥HV-68 were 2.9% (2.1%) p56D bϩ and 4.5% (2.2%) IFN-␥ ϩ at 7 days after vacc-p56 infection, while Ͻ1% in either site were shown to be p79-specific after the comparable i.p.…”

“…Lymphocytes were washed in PBS͞BSA (0.1%)͞ azide (0.01%) and incubated for 30 min at room temperature with tetrameric complexes (14,23) of phycoerythrin (PE)-labeled H-2D b ϩ p56 (p56D b ) or H-2K b ϩ p56 (p79K b ), then stained on ice with a tricolor-conjugated mAb to CD8␣ (Caltag, Burlingame, CA). The cells were washed once after a 30-min incubation on ice, and analyzed (24) on a FACScan using CELLQUEST software (Becton Dickinson).…”

“…The CD8 ϩ T cell populations were cultured for 5 h in RPMI supplemented with penicillin (100 units͞ml), streptomycin (100 g͞ml), glutamine (2 mM), FCS (10%), and 5 g͞ml Brefeldin A (Epicentre Technologies, Madison, WI), in the presence or absence of 1 M of the p56 or p79 peptide (8,14). The cells were then stained with the FITC-conjugated mAb to CD8␣ (PharMingen), fixed in 1% formaldehyde, permeabilized with 0.5% saponin, and stained with a PE-conjugated mAb to IFN-␥ (PharMingen).…”

Perturbation of B Cell Activation in SLAM-Associated Protein-Deficient Mice Is Associated with Changes in Gammaherpesvirus Latency Reservoirs

“…It is not clear that the less than 2-fold differences in the levels of cytolysis of cells expressing a particular epitope have physiological relevance in terms of viral control and the establishment of latency. In addition, ␥HV68-specific CTL activity is complex in that we and others (41,54,55) have shown that peak levels of CD8 T cells specific for ORF6 and ORF61 vary differentially during the infection, corresponding to kinetic differences in levels of expression of the two lytic epitopes, and presentation of the epitopes by different cell types. Our observation that latency in total B cells at 5 and 10 dpi is unaffected by the SAP mutation, but is dramatically reduced in SAP-deficient mice at 15 dpi (Fig.…”

A Replication-Deficient Murine γ-Herpesvirus Blocked in Late Viral Gene Expression Can Establish Latency and Elicit Protective Cellular Immunity

“…We assessed cellular immunity elicited by ORF31STOP compared with wild-type ␥HV68 infection, using three different assays. First, we examined tetramer-positive T cells specific for two well-characterized lytic epitopes in C57BL/6 mice derived from ORF6 (ORF6 487-495 / D b ), which encodes a ssDNA binding protein, and ORF61 (ORF61 524 -531 /K b ), which encodes a ribonucleotide reductase (40), in both the lung and spleen following i.n. or i.p.…”