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 CD62Llow 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 Vbeta4+ CD8+ T cells, with the Vbeta4 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 CD62Llow CD8+ T lymphocytes than would be expected in peripheral blood, but fails to diminish the prominence of the V4beta+ 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.
Doherty
P C
PC
Department of lmmunology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA. <peter.doherty@stjude.org
Tripp
R A
RA
Hamilton-Easton
A M
AM
Cardin
R D
RD
Woodland
D L
DL
Blackman
M A
MA
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D000956:Antigens, Viral; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens