Results: 4

1.
Fig. 1

Fig. 1. From: A Vital Role For IL-21 in the Control of a Chronic Viral Infection.

Diminished IL-21+ CD4+ T cell responses during the initial phase of LCMV-Cl 13 infection. IL-21 and IFN-γ production by LCMV GP61-80 CD4+ T cells was determined eight days following LCMV-Arm or Cl 13 infections of B6 mice. (A) Flow cytometric analysis of intracellular staining for IL-21 and IFN-γ in splenocytes from LCMV infected Il21−/− and Il21+/+ mice after stimulation with GP61-80 peptide. Gated total CD4+ T cells are shown. (B) Enumeration of IL-21-producing CD4+ T cells at eight days after LCMV-Arm or Cl 13 infection. Graphs represent mean ± SD; ***P < 0.001. Representative results are shown from two independent experiments (n = 8–9 for Il21+/+ cohorts and n = 2 for Il21−/− mice).

John S. Yi, et al. Science. ;324(5934):1572-1576.
2.
Fig. 3

Fig. 3. From: A Vital Role For IL-21 in the Control of a Chronic Viral Infection.

IL-21 acts directly to sustain virus-specific CD8+ T cells during an ongoing infection. Cohorts of control Il21r+/+/IL21r+/+ (CD45.1/CD45.2) and experimental IL21r+/+/IL21r−/− (CD45.1/CD45.2) mixed bone-marrow chimeras were infected with LCMV-Cl 13 and CD8+ T cell responses evaluated over time. (A) PBMCs were evaluated by flow cytometry to check reconstitution of CD8+ T cells in Il21r+/+/Il21r+/+ or Il21r+/+/Il21r−/− mixed bone-marrow chimeras prior to infection. Gated CD8+ T cells are shown. (B) Flow cytometric analysis of GP33- and GP276-specific CD8+ T cell responses in the circulation at days eight and 16 after infection. Gated tetramer+ CD8+ T cells are shown. (C) Flow cytometric analysis of splenic CD8+ T cells and GP33- and GP276-specific responses at three weeks following infection. Gated CD8+ (left panel) or CD8+ tetramer+ (right panels) cells are shown. (D) Absolute numbers of GP33- and GP276-specific CD8+ T cells in mixed bone-marrow chimeras three weeks following infection. Graphs represent average + SD of Il21r+/+ CD45.1 CD8+ T cells (black), Il21r+/+ CD45.2 CD8+ T cells (gray) and Il21r−/− CD45.2 CD8 T cells (white). **P < 0.01, ***P < 0.001. Representative results are shown from one of two similar experiments (n= 7 and 8 for the Il21r+/+/IL21r+/+ and IL21r+/+/IL21r−/− cohorts, respectively)

John S. Yi, et al. Science. ;324(5934):1572-1576.
3.
Fig. 4

Fig. 4. From: A Vital Role For IL-21 in the Control of a Chronic Viral Infection.

IL-21 treatment enhances CD8+ T cell responses and reduces viral titers in Cd4−/− mice. LCMV-Cl 13 infected Cd4−/− mice were either left untreated or administered daily doses of 10μg recombinant IL-21 for eight days. At day nine after infection CD8+ T cell responses and viral loads were analyzed. (A) Flow cytometric analysis of intracellular staining of IFN-γ and IL-2 production in splenic virus-specific CD8+ T cells from control or treated cohorts. Gated CD8+ T cells are shown. The mean-fluorescence-intensity (MFI) of IFN-γ producing CD8+ T cells are reported in parentheses. (B) Flow cytometric analysis of GP33 and NP396 tetramer+ CD8+ T cells. Plots show gated CD8+ T cells. (C) Viral titers were assessed in the serum, lungs, and liver of control and IL-21-treated mice. Dotted line indicates the limit of detection (50 pfu/mL) for serum samples. *P < 0.05. Representative results from one of two independent experiments are shown (n= 7 and 6 for control and treated groups, respectively).

John S. Yi, et al. Science. ;324(5934):1572-1576.
4.
Fig. 2

Fig. 2. From: A Vital Role For IL-21 in the Control of a Chronic Viral Infection.

Severe CD8+ T cell exhaustion and viral persistence in the absence of IL-21. Splenic CD8+ T cell responses and viral titers were evaluated following LCMV-Cl 13 infection of Il21+/+, +/−, and −/− mice. (A) Flow cytometric analysis of intracellular cytokine staining for IFN-γ and IL-2 production by CD8+ T cells at eight days following infection after restimulation without or with the indicated peptide epitopes. Gated CD8+ T cells are shown and the percentages of CD8+, IFN-γ+ cells that co-produce IL-2 are reported in parentheses. (B) Percentages of epitope-specific CD8+, IFN-γ+ cells that coproduce IL-2 at eight days following infection. Error bars are SEM; * P<0.05 by comparison with Il21+/+ group. (C) Serum viral titers over time following LCMV-Cl 13 infection of Il21+/+, +/−, −/−, and Cd4−/− mice. Results from individual mice are shown; the dotted line represents the limit of detection. (D) IFN-γ and IL-2 production by LCMV-specific CD8+ T cells at 136 days following infection. Gated CD8+ T cells are shown. (E and F) CD43 and PD-1 expression by GP33 tetramer+ CD8+ T cells from Il21+/+ (shaded), +/− (dashed line), and −/− (bold line) mice at eight (E) and 136 days (F) post-infection. The Il21+/− data shown in (D) and (F) are from mice that were aviremic at the time of analysis. Representative or composite data are shown from two independent experiments (n=3–6).

John S. Yi, et al. Science. ;324(5934):1572-1576.

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