TUNING INTO IMMUNOLOGICAL DISSONANCE - AN EXPERIMENTAL-MODEL FOR INFECTIOUS-MONONUCLEOSIS

Virus infections cause a much more profound perturbation of the lympho id tissue than can be accounted for by the exigencies of the antigen-s pecific response. The extent of this 'immunological dissonance' is see n most dramatically in mice infected with a persistent gamma-herpesvir us, MHV-68. A profile of massive, continuing proliferation of both T a nd B cells in the lymph nodes and spleen leads to a dramatic increase in the prevalence of a CD62L(low) CD8(+) T cell subset in the blood, a pattern first detected two to three weeks after intranasal exposure t o the inducing virus. This syndrome, which seems identical to human in fectious mononucleosis (IM), persists for a further month or more. Par t of the IM-like phase of MHV-68 infection reflects the selective expa nsion of V beta 4(+) CD8(+) T cells, with the V beta 4 effect being ap parent for several different MHC class I H-2 types but-not in mice tha t are deficient in MHC class II glycoprotein expression. Depleting CD4 (+) T helper cells in MHV-68-infected mice leads to the decreased prol iferation of the CD8(+) T cells in the spleen and fewer CD62L(low) CD8 (+) T lymphocytes than would be expected in peripheral blood, but fail s to diminish the prominence of the V4 beta(+) CD8(+) population. The results so far of this unique experimental mouse model of IM suggest t hat both cytokine-mediated effects and a viral superantigen are operat ing to promote the dramatic expansion and persistence of activated CD8 (+) T cells in the vascular compartment.