J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/05/1641/10 $2.00
Volume 185, Number 9, May 5, 1997 1641-1650

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

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

From the ^* Department of Immunology,  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 -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 V4⁺ phenotype. Interestingly, the V4 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 V4 bias of the T cells, the V4⁺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 V4⁺CD8⁺ T cells.

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