Tuning into immunological dissonance: an experimental model for infectious mononucleosis

Virus infections cause a much more profound perturbation of the lymphoid tissue than can be accounted for by the exigencies of the antigen-specific response. The extent of this 'immunological dissonance' is seen most dramatically in mice infected with a persistent gamma-herpesvirus, MHV-68. A profile of massive, continuing proliferation of both T and 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 to the inducing virus. This syndrome, which seems identical to human infectious mononucleosis (IM), persists for a further month or more. Part of the IM-like phase of MHV-68 infection reflects the selective expansion of V beta 4(+) CD8(+) T cells, with the V beta 4 effect being apparent for several different MHC class I H-2 types but-not in mice that are deficient in MHC class II glycoprotein expression. Depleting CD4(+) T helper cells in MHV-68-infected mice leads to the decreased proliferation of the CD8(+) T cells in the spleen and fewer CD62L(low) CD8(+) T lymphocytes than would be expected in peripheral blood, but fails to diminish the prominence of the V4 beta(+) CD8(+) population. The results so far of this unique experimental mouse model of IM suggest that both cytokine-mediated effects and a viral superantigen are operating to promote the dramatic expansion and persistence of activated CD8(+) T cells in the vascular compartment.