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A crucial role for B and T lymphocyte attenuator in preventing the development of CD4+ T cell-mediated herpetic stromal keratitis.

Xia L, Zhang S, Zhou J, Li Y - Mol. Vis. (2010)

Bottom Line: Systemic administration of pBTLA resulted in a diminished incidence and severity of corneal lesions compared to controls.The results suggest that recombinant pBTLA plays a crucial role in preventing HSV-1 specific responses in CD4(+) Th1 cells in the infected corneas.Thus, BTLA, with immunosuppressive effects, may be a good candidate for treatment of HSK.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, People's Republic of China. xialk@sjhospital.org

ABSTRACT

Purpose: To investigate the effect of the B and T lymphocyte attenuator (BTLA; CD272) on cluster of differentiation (CD)4(+) T cell-mediated corneal immunopathology during murine herpetic stromal keratitis (HSK).

Methods: BALB/c mice were infected with the herpes simplex virus type 1 (HSV-1) KOS strain by corneal scarification. The levels of BTLA expression in CD4(+) and CD8(+) T cells in murine peripheral blood were determined by flow cytometry on days 0, 3, 7, 10, 14, and 21 after HSV-1 infection. BTLA expression in the infected cornea was detected by immunohistochemistry. BALB/c mice were injected intraperitoneally with recombinant plasmid DNA encoding BTLA (pBTLA), pcDNA3.1, or PBS on 0 and 7 days before infection and 7 days postinfection. The incidence and severity of stromal disease, tear film virus titers, and the delayed-type hypersensitivity (DTH) reaction were then compared among treated and control groups. The effects of pBTLA on CD4(+) T cells that infiltrated into infected corneas and on type 1 helper T-cell (Th1) cytokines (interferon-gamma [IFN-γ]) were evaluated. The levels of glycoprotein D (gD) mRNA in corneas were tested by real-time PCR. The eyes were examined histologically.

Results: BTLA expression increased both in the corneas of HSV-1 infected mice and in CD4(+) T cells in the murine peripheral blood. Systemic administration of pBTLA resulted in a diminished incidence and severity of corneal lesions compared to controls. Treatment with pBTLA led to a decreased infiltration of CD4(+) T cells into infected corneas, and diminished Th1 responses in murine corneas, draining lymph nodes, and splenocytes. The pBTLA treated mice showed an impaired DTH response two weeks after HSV-1 infection compared to control mice. No differences were noted in tear film virus titers or gD mRNA levels in corneas among the experimental groups.

Conclusions: The results suggest that recombinant pBTLA plays a crucial role in preventing HSV-1 specific responses in CD4(+) Th1 cells in the infected corneas. Thus, BTLA, with immunosuppressive effects, may be a good candidate for treatment of HSK.

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Related in: MedlinePlus

pBTLA plasmid treatment suppresses the systemic DTH responses of mice. pBTLA and pcDNA3.1 treated mice received 100 µg of the respective plasmid on days −7, 0, 7 relative to HSV-1 corneal inoculation, PBS treated mice received 100 µl PBS i.p. Two weeks after viral infection, DTH responses were measured in the footpad. All infected groups (n=6 in each group) had significant responses compared with the uninfected control mice (*p<0.01). DTH responses in pBTLA treated mice were lower than in pcDNA3.1 or PBS control mice (#p<0.01).
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f7: pBTLA plasmid treatment suppresses the systemic DTH responses of mice. pBTLA and pcDNA3.1 treated mice received 100 µg of the respective plasmid on days −7, 0, 7 relative to HSV-1 corneal inoculation, PBS treated mice received 100 µl PBS i.p. Two weeks after viral infection, DTH responses were measured in the footpad. All infected groups (n=6 in each group) had significant responses compared with the uninfected control mice (*p<0.01). DTH responses in pBTLA treated mice were lower than in pcDNA3.1 or PBS control mice (#p<0.01).

Mentions: The DTH responses of the footpad in the different mice groups two weeks after viral infection are shown in Figure 7. The DTH responses in all infected groups were significantly higher than uninfected controls (p<0.01). In addition, DTH responses in pBTLA treated mice were lower than in pcDNA3.1 or PBS treated mice (p<0.01). The results indicated that pBTLA treatment inhibited immune cell-mediated inflammation induced by HSV-1.


A crucial role for B and T lymphocyte attenuator in preventing the development of CD4+ T cell-mediated herpetic stromal keratitis.

Xia L, Zhang S, Zhou J, Li Y - Mol. Vis. (2010)

pBTLA plasmid treatment suppresses the systemic DTH responses of mice. pBTLA and pcDNA3.1 treated mice received 100 µg of the respective plasmid on days −7, 0, 7 relative to HSV-1 corneal inoculation, PBS treated mice received 100 µl PBS i.p. Two weeks after viral infection, DTH responses were measured in the footpad. All infected groups (n=6 in each group) had significant responses compared with the uninfected control mice (*p<0.01). DTH responses in pBTLA treated mice were lower than in pcDNA3.1 or PBS control mice (#p<0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965573&req=5

f7: pBTLA plasmid treatment suppresses the systemic DTH responses of mice. pBTLA and pcDNA3.1 treated mice received 100 µg of the respective plasmid on days −7, 0, 7 relative to HSV-1 corneal inoculation, PBS treated mice received 100 µl PBS i.p. Two weeks after viral infection, DTH responses were measured in the footpad. All infected groups (n=6 in each group) had significant responses compared with the uninfected control mice (*p<0.01). DTH responses in pBTLA treated mice were lower than in pcDNA3.1 or PBS control mice (#p<0.01).
Mentions: The DTH responses of the footpad in the different mice groups two weeks after viral infection are shown in Figure 7. The DTH responses in all infected groups were significantly higher than uninfected controls (p<0.01). In addition, DTH responses in pBTLA treated mice were lower than in pcDNA3.1 or PBS treated mice (p<0.01). The results indicated that pBTLA treatment inhibited immune cell-mediated inflammation induced by HSV-1.

Bottom Line: Systemic administration of pBTLA resulted in a diminished incidence and severity of corneal lesions compared to controls.The results suggest that recombinant pBTLA plays a crucial role in preventing HSV-1 specific responses in CD4(+) Th1 cells in the infected corneas.Thus, BTLA, with immunosuppressive effects, may be a good candidate for treatment of HSK.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, People's Republic of China. xialk@sjhospital.org

ABSTRACT

Purpose: To investigate the effect of the B and T lymphocyte attenuator (BTLA; CD272) on cluster of differentiation (CD)4(+) T cell-mediated corneal immunopathology during murine herpetic stromal keratitis (HSK).

Methods: BALB/c mice were infected with the herpes simplex virus type 1 (HSV-1) KOS strain by corneal scarification. The levels of BTLA expression in CD4(+) and CD8(+) T cells in murine peripheral blood were determined by flow cytometry on days 0, 3, 7, 10, 14, and 21 after HSV-1 infection. BTLA expression in the infected cornea was detected by immunohistochemistry. BALB/c mice were injected intraperitoneally with recombinant plasmid DNA encoding BTLA (pBTLA), pcDNA3.1, or PBS on 0 and 7 days before infection and 7 days postinfection. The incidence and severity of stromal disease, tear film virus titers, and the delayed-type hypersensitivity (DTH) reaction were then compared among treated and control groups. The effects of pBTLA on CD4(+) T cells that infiltrated into infected corneas and on type 1 helper T-cell (Th1) cytokines (interferon-gamma [IFN-γ]) were evaluated. The levels of glycoprotein D (gD) mRNA in corneas were tested by real-time PCR. The eyes were examined histologically.

Results: BTLA expression increased both in the corneas of HSV-1 infected mice and in CD4(+) T cells in the murine peripheral blood. Systemic administration of pBTLA resulted in a diminished incidence and severity of corneal lesions compared to controls. Treatment with pBTLA led to a decreased infiltration of CD4(+) T cells into infected corneas, and diminished Th1 responses in murine corneas, draining lymph nodes, and splenocytes. The pBTLA treated mice showed an impaired DTH response two weeks after HSV-1 infection compared to control mice. No differences were noted in tear film virus titers or gD mRNA levels in corneas among the experimental groups.

Conclusions: The results suggest that recombinant pBTLA plays a crucial role in preventing HSV-1 specific responses in CD4(+) Th1 cells in the infected corneas. Thus, BTLA, with immunosuppressive effects, may be a good candidate for treatment of HSK.

Show MeSH
Related in: MedlinePlus