Impact of asymptomatic Herpes simplex virus-2 infection on T cell phenotype and function in the foreskin

Prodger, Jessica L.; Gray, Ronald H.; Kigozi, Godfrey; Nalugoda, Fred; Galiwango, Ronald M.; Kighoma, Nehemiah; Kakanga, Moses; Hirbod, Taha; Wawer, Maria J.; Sewankambo, Nelson; Serwadda, David; Kaul, Rupert

doi:10.1097/qad.0b013e328354675c

Cited by 26 publications

(27 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3F; P ϭ 0.0452). These observations are consistent with the previously reported activated phenotype of CD4 ϩ T cells in foreskin in human subjects (12). To evaluate the potential impact of immunization with Ad26 and Ad35 vectors on foreskin inflammation, we compared the degree of foreskin immune cell activation between vaccinated animals and sham-immunized controls 1 year after immunization using multiparameter flow cytometry, immunohistochemistry, and ICS.…”

Section: Foreskin Is Highly Enriched With Memory Cd4supporting

confidence: 75%

“…We isolated ϳ10 6 mononuclear cells per foreskin specimen, which is consistent with the relative paucity of mononuclear cells in foreskin in humans (12). We observed decreased naive CD4 ϩ and CD8…”

Section: Foreskin Is Highly Enriched With Memory Cd4supporting

confidence: 60%

“…The reason for this observation remains unclear but may relate in part to the response of immune cells to foreskin microbiota (22)(23)(24). Foreskin CD4 ϩ T cells in humans are highly activated, potentially increasing the risk of HIV-1 acquisition in men (12). A trend toward increased HIV-1 acquisition among uncircumcised and Ad5 seropositive vaccine recipients in the Merck phase 2b…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that CD4 ϩ T cells in foreskin in humans are highly activated, potentially contributing to the risk of HIV-1 infection by increased HIV-1 target cells (12). It is therefore important to assess both antigen-specific immune responses and inflammation in foreskin following vaccination.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Balandya

Miller

Beck

et al. 2014

J Virol

View full text Add to dashboard Cite

Foreskin is the principal site of heterosexual HIV-1 infection in men. However, little is known about HIV-1-specific immune responses or inflammation in foreskin. To the best of our knowledge, no previous studies have assessed immune responses to candidate HIV-1 vaccines in foreskin. Using the rhesus monkey model, we show that intramuscular immunization with adenovirus serotype 26 and 35 vectors expressing SIV antigens elicited durable SIV Gag-specific CD4؉ and CD8 ؉ T cell responses in foreskin that were detectable for more than 1 year following vaccination. Gag-specific CD4؉ and CD8 ؉ T cells were also detectable in foreskin of SIV-and SHIV-infected animals and were at least comparable in magnitude to those in peripheral blood. However, unlike peripheral blood T cells, the majority of foreskin T cells exhibited transitional memory or effector memory phenotype and expressed higher levels of the activation markers CD69, HLA-DR, and CCR5, although vaccination did not further enhance foreskin CD4 ؉ T cell activation. These findings suggest that systemic vaccination strategies can elicit potentially important SIV-specific cellular immunity in foreskin. Further characterization of vaccine-elicited immune responses and inflammation in foreskin is warranted. IMPORTANCEWe demonstrate here the induction of SIV-specific cellular immune responses in foreskin by adenovirus serotype 26 and 35 vaccine vectors. Foreskin T cells were more activated than peripheral blood T cells, but foreskin T cells were not further activated by vaccination. These findings suggest that alternative serotype adenovirus vectors induce potentially important immune responses in foreskin.

show abstract

Section: Foreskin Is Highly Enriched With Memory Cd4supporting

confidence: 75%

Section: Foreskin Is Highly Enriched With Memory Cd4supporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Balandya

Miller

Beck

et al. 2014

J Virol

View full text Add to dashboard Cite

show abstract

“…Asymptomatic HSV-2 infection is also associated with T cell alterations in the genital mucosa (3,5,6), an increased expression of CD69 and CCR5 by endocervical CD4 + T cells (3), and increased CD4 + T cell density (7) and CCR5 expression by CD4 + T cells (6) in the foreskin. Because CCR5 + T cells are the primary target for sexually transmitted R5-tropic strains of HIV (8), this increased density of target cells in the genital mucosa may be an important contributor to the increased HIV susceptibility observed in asymptomatic HSV-2 infection.…”

mentioning

confidence: 99%

Impact of Asymptomatic Herpes Simplex Virus Type 2 Infection on Mucosal Homing and Immune Cell Subsets in the Blood and Female Genital Tract

Shannon

Thomas-Pavanel

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

HSV-2 infection is common and generally asymptomatic, but it is associated with increased HIV susceptibility and disease progression. This may relate to herpes-mediated changes in genital and systemic immunology. Cervical cytobrushes and blood were collected from HIV-uninfected African/Caribbean women in Toronto, and immune cell subsets were enumerated blindly by flow cytometry. Immune differences between groups were assessed by univariate analysis and confirmed using a multivariate model. Study participants consisted of 46 women, of whom 54% were infected with HSV-2. T cell activation and expression of the mucosal homing integrin α4β7 (19.60 versus 8.76%; p < 0.001) were increased in the blood of HSV-2–infected women. Furthermore, expression of α4β7 on blood T cells correlated with increased numbers of activated (coexpressing CD38/HLA-DR; p = 0.004) and CCR5+ (p = 0.005) cervical CD4+ T cells. HSV-2–infected women exhibited an increase in the number of cervical CD4+ T cells (715 versus 262 cells/cytobrush; p = 0.016), as well as an increase in the number and proportion of cervical CD4+ T cells that expressed CCR5+ (406 versus 131 cells, p = 0.001; and 50.70 versus 34.90%, p = 0.004) and were activated (112 versus 13 cells, p < 0.001; and 9.84 versus 4.86%, p = 0.009). Mannose receptor expression also was increased on cervical dendritic cell subsets. In conclusion, asymptomatic HSV-2 infection was associated with significant systemic and genital immune changes, including increased immune activation and systemic α4β7 expression; correlation of the latter with highly HIV-susceptible CD4+ T cell subsets in the cervix may provide a mechanism for the increased HIV susceptibility observed in asymptomatic HSV-2–infected women.

show abstract

Inflammation and HIV Transmission in Sub-Saharan Africa

et al. 2015

Self Cite

View full text Add to dashboard Cite

While the per-contact risk of sexual HIV transmission is relatively low, it is fourfold higher in sub-Saharan Africa, and this may partly explain the major global disparities that exist in HIV prevalence. Genital immune parameters are key determinants of HIV transmission risk, including epithelial integrity and the presence of highly HIV-susceptible intraepithelial or submucosal CD4+ T cell target cells. Biological parameters that may enhance mucosal HIV susceptibility in highly HIV-affected regions of sub-Saharan Africa include increased levels of mucosal inflammation, which can affect both epithelial integrity and target cell availability, as well as the increased mucosal surface area that is afforded by an intact foreskin, contraceptive choices, and intravaginal practices. There are multifactorial causes for increased mucosal inflammation, with the prevalence and nature of common co-infections being particularly relevant.

show abstract

Impact of asymptomatic Herpes simplex virus-2 infection on T cell phenotype and function in the foreskin

Cited by 26 publications

References 14 publications

Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Impact of Asymptomatic Herpes Simplex Virus Type 2 Infection on Mucosal Homing and Immune Cell Subsets in the Blood and Female Genital Tract

Inflammation and HIV Transmission in Sub-Saharan Africa

Contact Info

Product

Resources

About