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© The Rockefeller University Press, 0022-1007/1997/5/1641/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 9, May 5, 1997 1641-1650

Articles

Pathogenesis of an Infectious Mononucleosis-like Disease Induced by a Murine {gamma}-Herpesvirus: Role for a Viral Superantigen?

Ralph A. Tripp*, Ann Marie Hamilton-Easton*, Rhonda D. Cardin*, Phuong Nguyen*, Frederick G. Behm{ddagger}, David L. Woodland*,||, Peter C. Doherty*,§,||, and Marcia A. Blackman*,||

From the * Department of Immunology, {ddagger} Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105; and the § Department of Pediatrics, || Department of Pathology, University of Tennessee, Memphis, Tennessee 38163

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 (CD62Llo) in the peripheral blood increased greater than fourfold by 21 d after infection of C57BL/6J (H-2b) 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 Vβ4+ phenotype. Interestingly, the Vβ4 dominance was also seen, to varying extents, in H-2k, H-2d, H-2u, and H-2q strains of mice. In addition, although CD4 depletion from day 11 had no effect on the Vβ4 bias of the T cells, the Vβ4+CD8+ expansion was absent in H-2IAb–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 Vβ4+CD8+ T cells.

Address correspondence to Marcia A. Blackman, Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105.

These experiments were supported by National Institutes of Health grants CA21765, AI38349, P30 CA21765, and by the American Lebanese Syrian Associated Charities.

1Abbreviations used in this paper: {gamma}HV, {gamma}-herpesvirus; CTLp, CTL precursor; IM, infectious mononucleosis; MHV-68, murine {gamma}-herpesvirus 68; MMTV, mouse mammary tumor virus.

Peter C. Doherty and Marcia A. Blackman made equal contributions to this manuscript.


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