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Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen?

Tripp RA, Hamilton-Easton AM, Cardin RD, Nguyen P, Behm FG, Woodland DL, Doherty PC, Blackman MA - J. Exp. Med. (1997)

Bottom Line: 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 Vbeta4+ phenotype.In addition, although CD4 depletion from day 11 had no effect on the Vbeta4 bias of the T cells, the Vbeta4+CD8+ expansion was absent in H-2IA(b)-deficient congenic mice.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 Vbeta4+CD8+ T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

ABSTRACT
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 (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 Vbeta4+ phenotype. Interestingly, the Vbeta4 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 Vbeta4 bias of the T cells, the Vbeta4+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 Vbeta4+CD8+ T cells.

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Related in: MedlinePlus

TCR-Vβ usage. TCR-Vβ usage in CD8+ T cells isolated  from peripheral blood (A) and spleen (B) of MHV-68–infected (closed  bars) and uninfected (open bars) B6 mice analyzed 21 d after infection was  determined by two-color staining using a panel of Vβ-specific mAb and  anti-CD8. The data are expressed as the percentage of CD8+ T cells expressing a particular TCR-Vβ among total CD8+ T cells.
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Figure 3: TCR-Vβ usage. TCR-Vβ usage in CD8+ T cells isolated from peripheral blood (A) and spleen (B) of MHV-68–infected (closed bars) and uninfected (open bars) B6 mice analyzed 21 d after infection was determined by two-color staining using a panel of Vβ-specific mAb and anti-CD8. The data are expressed as the percentage of CD8+ T cells expressing a particular TCR-Vβ among total CD8+ T cells.

Mentions: As a first step in determining the mechanism of T cell activation, the TCR-Vβ profile was examined. The results showed a striking predominance of Vβ4+ T cells among the CD8+ T cells in the peripheral blood, and a compensatory decrease in all other Vβs (Fig. 3 A). This Vβ4 expansion was also seen in splenic CD8+ T cells (Fig. 3 B), but not in peripheral lymph nodes (data not shown). The Vβ4 expansion among the CD8+ peripheral blood T cells was not evident in the first 2 wk of infection, but was consistently seen at day 21 after infection, although the magnitude of the increase varied in individual B6 mice (Fig. 4 A). A variable and much reduced Vβ4 expansion was also transiently observed in CD4+ T cells from peripheral blood (Fig. 4 B) and spleen (data not shown). Elevated levels of Vβ4+CD8+ T cells were still observed at 90 d after infection (Fig. 4 A).


Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen?

Tripp RA, Hamilton-Easton AM, Cardin RD, Nguyen P, Behm FG, Woodland DL, Doherty PC, Blackman MA - J. Exp. Med. (1997)

TCR-Vβ usage. TCR-Vβ usage in CD8+ T cells isolated  from peripheral blood (A) and spleen (B) of MHV-68–infected (closed  bars) and uninfected (open bars) B6 mice analyzed 21 d after infection was  determined by two-color staining using a panel of Vβ-specific mAb and  anti-CD8. The data are expressed as the percentage of CD8+ T cells expressing a particular TCR-Vβ among total CD8+ T cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196306&req=5

Figure 3: TCR-Vβ usage. TCR-Vβ usage in CD8+ T cells isolated from peripheral blood (A) and spleen (B) of MHV-68–infected (closed bars) and uninfected (open bars) B6 mice analyzed 21 d after infection was determined by two-color staining using a panel of Vβ-specific mAb and anti-CD8. The data are expressed as the percentage of CD8+ T cells expressing a particular TCR-Vβ among total CD8+ T cells.
Mentions: As a first step in determining the mechanism of T cell activation, the TCR-Vβ profile was examined. The results showed a striking predominance of Vβ4+ T cells among the CD8+ T cells in the peripheral blood, and a compensatory decrease in all other Vβs (Fig. 3 A). This Vβ4 expansion was also seen in splenic CD8+ T cells (Fig. 3 B), but not in peripheral lymph nodes (data not shown). The Vβ4 expansion among the CD8+ peripheral blood T cells was not evident in the first 2 wk of infection, but was consistently seen at day 21 after infection, although the magnitude of the increase varied in individual B6 mice (Fig. 4 A). A variable and much reduced Vβ4 expansion was also transiently observed in CD4+ T cells from peripheral blood (Fig. 4 B) and spleen (data not shown). Elevated levels of Vβ4+CD8+ T cells were still observed at 90 d after infection (Fig. 4 A).

Bottom Line: 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 Vbeta4+ phenotype.In addition, although CD4 depletion from day 11 had no effect on the Vbeta4 bias of the T cells, the Vbeta4+CD8+ expansion was absent in H-2IA(b)-deficient congenic mice.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 Vbeta4+CD8+ T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

ABSTRACT
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 (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 Vbeta4+ phenotype. Interestingly, the Vbeta4 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 Vbeta4 bias of the T cells, the Vbeta4+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 Vbeta4+CD8+ T cells.

Show MeSH
Related in: MedlinePlus