Reduced functional capacity of CD8+ T cells expanded by post-exposure vaccination of gamma-herpesvirus-infected CD4-deficient mice.
Mice (I-A(b-/-)) that lack CD4(+) T cells remain healthy for at least three months after respiratory exposure to the murine gamma-herpesvirus 68 (gammaHV68), then succumb with symptoms of chronic wasting disease. Postexposure challenge of gammaHV68-infected I-A(b+/+) and I-A(b-/-) mice with a recombinant vaccinia virus (Vacc-p56) expressing an antigenic gammaHV68 peptide caused a massive increase in the numbers of D(b)p56-specific CD8(+) T cells. Previous experiments showed that, despite the large numbers of potential CTL effectors, there was little effect on the long-term survival of the CD4-deficient group and no diminution in the level of persistent virus shedding and latency. Comparison of the expanded CD8(+)D(b)p56(+) sets in the I-A(b+/+) and I-A(b-/-) mice indicated that these two T cell populations were not identical. More CD69(high)CD8(+) D(b)p56(+) T cells were found in the CD4-deficient mice, an effect that might be thought to reflect higher Ag load. By contrast, the mean fluorescence intensity of staining for the CD44 glycoprotein was diminished on CD8(+)D(b)p56(+) T cells from the I-A(b-/-) group, the level of CTL activity was lower on a per cell basis, and the relative prevalence of IFN-gamma(+)TNF-alpha(+) T cells detected after in vitro stimulation with the p56 peptide was decreased. Given that this experimental system provides an accessible model for evaluating postexposure vaccination protocols that might be used in diseases like HIV/AIDS, the further need is to clarify the underlying molecular mechanisms and the relative significance of lack of CD4(+) T help vs higher Ag load for these expanded CD8(+) effector populations.
Liu
Haiyan
H
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. haiyan.liu@stjude.org
Andreansky
Samita
S
Diaz
Gabriela
G
Hogg
Twala
T
Doherty
Peter C
PC
D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology*; D006183:H-2 Antigens / Q000096:biosynthesis; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006183:H-2 Antigens; D022283:Herpesvirus Vaccines; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; C064828:Sta56 antigen, Rickettsia tsutsugamushi; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D007371:Interferon-gamma