Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen?
The murine gamma-herpesvirus 68 has many similarities to EBV, and induces a syndrome comparable to infectious mononucleosis (IM). The frequency of activated CD8+ T cells (CD62L(lo)) in the peripheral blood increased greater than fourfold by 21 d after infection of C57BL/6J (H-2(b)) mice, and remained high for at least a further month. The spectrum of T cell receptor usage was greatly skewed, with as many as 75% of the CD8+ T cells in the blood expressing a Vbeta4+ phenotype. Interestingly, the Vbeta4 dominance was also seen, to varying extents, in H-2(k), H-2(d), H-2(u), and H-2(q) strains of mice. In addition, although CD4 depletion from day 11 had no effect on the Vbeta4 bias of the T cells, the Vbeta4+CD8+ expansion was absent in H-2IA(b)-deficient congenic mice. However, the numbers of cycling cells in the CD4 antibody-depleted mice and mice that are CD4 deficient as a consequence of the deletion of MHC class II, were generally lower. The findings suggest that the IM-like disease is driven both by cytokines provided by CD4+ T cells and by a viral superantigen presented by MHC class II glycoproteins to Vbeta4+CD8+ T cells.
Tripp
R A
RA
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Hamilton-Easton
A M
AM
Cardin
R D
RD
Nguyen
P
P
Behm
F G
FG
Woodland
D L
DL
Doherty
P C
PC
Blackman
M A
MA
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002453:Cell Cycle; D004195:Disease Models, Animal; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007244:Infectious Mononucleosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D013154:Spleen / Q000166:cytology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens