title: Effects of HIV-1 and herpes simplex virus type 2 infection on lymphocyte and dendritic cell density in adult foreskins from Rakai, Uganda.
abstract: 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/mm(2)), CD4(+) T cell densities were similar in the HIV-infected, HSV-2-infected group (mean, 28.7 cells/mm(2)), 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Johnson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Aleisha N
authors.initials: AN
authors.lastname: Collinson-Streng
authors.forename: Toby
authors.initials: T
authors.lastname: Cornish
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Kong
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tsai
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Godfrey
authors.initials: G
authors.lastname: Kigozi
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D002452:Cell Count; D002944:Circumcision, Male; D003713:Dendritic Cells / Q000166:cytology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D052816:Foreskin / Q000166:cytology* / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006558:Herpes Genitalis / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology / Q000821:virology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology* / Q000821:virology; D014454:Uganda; D055815:Young Adult