Effects of HIV-1 and Herpes Simplex Virus Type 2 Infection on Lymphocyte and Dendritic Cell Density in Adult Foreskins from Rakai, Uganda

• Published in: The Journal of infectious diseases 2011-03, Vol.203 (5), p.602-609
• Main Authors: Johnson, Kristine E., Redd, Andrew D., Quinn, Thomas C., Collinson-Streng, Aleisha N., Cornish, Toby, Kong, Xiangrong, Sharma, Rajni, Tobian, Aaron A. R., Tsai, Benjamin, Sherman, Mark E., Kigozi, Godfrey, Serwadda, David, Wawer, Maria J., Gray, Ronald H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - virology; Cell Count; Circumcision, Male; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - virology; Enzyme-Linked Immunosorbent Assay; Epidermal cells; Foreskin; Foreskin - cytology; Foreskin - pathology; Foreskin - virology; Fundamental and applied biological sciences. Psychology; Herpes Genitalis - pathology; Herpes Genitalis - prevention & control; Herpes Genitalis - virology; Herpes simplex virus 2; Herpesvirus 2, Human - isolation & purification; HIV; HIV 1; HIV Infections - pathology; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - isolation & purification; Human herpesvirus 2; Human immunodeficiency virus; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Humans; Immunohistochemistry; Infections; Infectious diseases; Inflammation; Inflammation - pathology; Inflammation - virology; Islets of Langerhans; Linear Models; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - virology; Uganda; Virology; VIRUSES; Young Adult
• ISSN: 0022-1899; 1537-6613; 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiq091

Background. Male circumcision reduces human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2) acquisition, and HSV-2 infection is associated with an increased risk of HIV acquisition. To assess the cellular basis for these associations, we estimated immunologic cellular densities in foreskin tissue. Methods. Immunostained CD1a⁺ dendritic cell and CD4⁺ and CD8⁺ T cell densities were quantified in foreskin samples obtained from medical circumcision in Rakai, Uganda (35 HIV-infected, HSV-2-infected men; 5 HIV-infected, HSV-2-uninfected men; 22 HIV-uninfected, HSV-2-infected men; and 29 HIV-uninfected, HSV-2-uninfected men. Results. CD1A⁺ dendritic cell densities did not vary by HIV or HSV-2 status. Compared with densities in HIV-uninfected, HSV-2-uninfected men (mean, 26.8 cells/mm²), CD4⁺ T cell densities were similar in the HIV-infected, HSV-2-infected group (mean, 28.7 cells/mm²), were significantly decreased in the HIV-infected, HSV-2-uninfected group (mean, 11.2; P < .05), and were increased in the HIV-uninfected, HSV-2-infected group (mean, 68.7; P < .05). Dermal CD8⁺ T cell densities were higher in the HIV and HSV-2-coinfected group (mean, 102.9) than in the HIV-uninfected, HSV-2-uninfected group (mean, 10.0; P < .001), the HIV-infected, HSV-2-uninfected group (mean, 27.3; P < .001), and the HIV-uninfected, HSV-2-infected group (mean, 25.3; P < .005). Discussion. The increased CD4⁺ cellular density in the HIV-uninfected, HSV-2-infected men may help to explain why HSV-2—infected men are at increased risk of HIV acquisition. The absence of this increase in men coinfected with both HIV and HSV-2 is likely in part the result of the progressive loss of CD4⁺ cells in HIV infection. Conversely, HIV and HSV-2 coinfection appears to synergistically increase CD8⁺ T cell densities.