Abnormal Immune Responses to Herpes Simplex in Subjects with Atopic Dermatitis Complicated by Eczema Herpeticum

RATIONALE: The basis for increased propensity of atopic dermatitis (AD) patients to develop severe viral infections such as eczema herpeticum (EH+) is poorly understood. We investigated immune responses (ex vivo) of ADEH+ vs AD without history of EH (ADEH-) or normal controls (NC) to herpes simplex virus (HSV) to gain a better understanding of their increased susceptibility to HSV infection.METHODS: One to 65 yr old subjects with ADEH+ (n = 13), ADEH- (n = 15), or NC (n = 18) were enrolled. Cell mediated immunity (CMI) analyses on peripheral blood mononuclear cells (PBMC) included: HSV-specific CMI responses by evaluating IFNγ production post-HSV stimulation using enzyme-linked immunosorbent spot (ELISPOT) technology, flow cytometry of HSV-specific total, CD4, or CD8 IFNγ expressing cells, and other T cell subsets relevant to generation of viral-specific cytotoxic T cells.RESULTS: Post-HSV stimulation, IFNγ production was found to be lower across AD (mean = 98 ± 1.16) compared to NC (mean = 270 ± 1.20; p < 0.001). Using flow cytometry, IFNγ expression was reduced in CD4 (p = 0.046) and CD8 (p = 0.005) subsets of AD compared to NC, but there was no difference between ADEH+ and ADEH-. However, CD14+ cells from ADEH+ had greater IL-10 expression (p = 0.005) and proportionately less IFNγ to IL-10 expression compared to ADEH- subjects (p = 0.094). No differences were seen in IL-13 and IL-17 expression in T cell subsets.CONCLUSIONS: AD patients have reduced HSV-induced IFNγ producing cells, which are important cytotoxic effectors of immune-protection against viruses. ADEH+, compared to ADEH-, subjects have increased expression of IL-10 in CD14+ cells. This may contribute to increased susceptibility to severe viral infections. RATIONALE: The basis for increased propensity of atopic dermatitis (AD) patients to develop severe viral infections such as eczema herpeticum (EH+) is poorly understood. We investigated immune responses (ex vivo) of ADEH+ vs AD without history of EH (ADEH-) or normal controls (NC) to herpes simplex virus (HSV) to gain a better understanding of their increased susceptibility to HSV infection. METHODS: One to 65 yr old subjects with ADEH+ (n = 13), ADEH- (n = 15), or NC (n = 18) were enrolled. Cell mediated immunity (CMI) analyses on peripheral blood mononuclear cells (PBMC) included: HSV-specific CMI responses by evaluating IFNγ production post-HSV stimulation using enzyme-linked immunosorbent spot (ELISPOT) technology, flow cytometry of HSV-specific total, CD4, or CD8 IFNγ expressing cells, and other T cell subsets relevant to generation of viral-specific cytotoxic T cells. RESULTS: Post-HSV stimulation, IFNγ production was found to be lower across AD (mean = 98 ± 1.16) compared to NC (mean = 270 ± 1.20; p < 0.001). Using flow cytometry, IFNγ expression was reduced in CD4 (p = 0.046) and CD8 (p = 0.005) subsets of AD compared to NC, but there was no difference between ADEH+ and ADEH-. However, CD14+ cells from ADEH+ had greater IL-10 expression (p = 0.005) and proportionately less IFNγ to IL-10 expression compared to ADEH- subjects (p = 0.094). No differences were seen in IL-13 and IL-17 expression in T cell subsets. CONCLUSIONS: AD patients have reduced HSV-induced IFNγ producing cells, which are important cytotoxic effectors of immune-protection against viruses. ADEH+, compared to ADEH-, subjects have increased expression of IL-10 in CD14+ cells. This may contribute to increased susceptibility to severe viral infections.