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. 2014 Sep 30;8:31–44. doi: 10.2174/1874613601408010031

Table 2.

Studies that examined target cell distribution in foreskin tissues.

STUDY SUBJECTS INDICATION FOR CIRCUMCISION STI STATUS RESULTS (LCs, CD4 T cells & Macrophages)  & CONCLUSIONS
Hussain, 1995 [19] 10 subjects, 7 subjects, 3-7 weeks
3 subjects, 7-36 years from London, UK		 Not Specified Not specified   LCs:    Infants: 41.9 ± 4.6 cells/mm2 in IFS, density in OFS not enumerated.              Older:  26.0 ± 5.7 cells/mm2 in IFS, density in OFS not enumerated.              No significant difference between IFS versus OFS terms of LC density (IFS = OFS).CD4+T cells:    Large number of CD4+T cells found in dermis and small number was found in       epidermis.                  Macrophages:   Found in dermis
Patterson, 2002 [7] 14 subjects, 10 months- 69 years from Chicago, USA Phimosis, balanitis, adhesions and redundant foreskins.   Not specified   LCs :   Significantly greater in IFS compared to OFSγ (IFS > OFS)              Majority of LCs found in epidermis (inner and outer).CD4+ T cells:  Significantly greater in IFS compared to OFSγ (IFS > OFS)                            Majority of CD4 T cells found in dermis.Macrophages:   percentage* of macrophages were similar in IFS and OFS.   Proportion of all 3 target cell types increase with age. History of balanitis/STIs significantly increased the number of target cells.
McCoombe, 2006 [6] 30 subjects,
9 cadaversf
(mean age 77.4 years)



21 subjectsf  (mean age 28.9 years)   8 penile necropsy specimens† from Melbourne, Australia
9 penile cadaveric specimens were obtained within 18 hours of death.


21 men were healthy and undergoing elective circumcision.		 HIV negative LCs :         61.3 cells/mm2 in IFS                   85.5 cells/mm2 in OFS                   56.0 cells/mm2 in frenulum          41.0 cells/mm2 in glans OFS > IFS > frenulum > glans > urethral meatus LC dendritic processes in IFS came within 4.8µm of epithelial surface compared to 20 µm in OFS.   CD4+ T cells:    Found in epidermis, but predominant in dermisγ. Macrophages:   Found in epidermis, but predominant in dermisγ.
Donoval, 2006 [23] 39 subjects, 18-24 years from  Kisumu, Kenya Foreskins obtained from the randomised controlled trial in Kenya [3]. 21 men without history of STI 19 men with a history of treated STI                        Epidermis †    Dermis † LC cells            1.23%           0.30 % CD4 T cells      0.08%           0.075% Macrophages    0.02%           0.04%  LC:   Mainly found in epidermisγ. CD4+ T cells:  No difference in the median percentages between epidermis and dermisγ.Macrophages:  Found predominantly in dermisγ.
Qi Qin, 2009 [11] 80 subjects, 60 subjects , 2-7 years           20 subjects, 20-29 years
from  Hangzhou, China

 
Group 1; circumcised for medical reasons related to UTI.

Group 2; circumcised for cultural and cosmetic reasons.
Adult men had no history of UTI. 		Not specified         LCs :   Children  UTI related            132.2 cells/mm2 in IFS,  131.7 cells/mm2 in OFS                              Non UTI related     87.5 cells/mm2  in IFS,  123.7  cells/mm2 in OFS             Adults                                     53.7 cells/mm2  in IFS,    88.3 cells/mm2 in OFS OFS > IFS of adults and healthy boys. OFS = IFS in boys with a history of infection.   CD4+ T cells:  Not specified Macrophages:  Not specified
Fischetti, 2009 [21] Subjectsfy (number of subjects or age range not specified) from London, UK Elective circumcisions after gender reassignment (after 6 weeks off hormonal therapy). Not specified   LCs :        230 cells/mm2 in IFS        170 cells/mm2 in OFS Exclusively reside in epidermis. The distance to dendritic projections of LCs from the epidermis surface Glans > IFS = OFS. Average number of LCs greatest for glans> IFS > OFS.   CD4+T cellsspan>:   260 cells/mm2 in IFS, 2.6 times higher than OFS.Typically present in dermis, infiltrate epidermis under inflammatory conditions. Average number of CD4+T cells greatest for glans> IFS > OFS.   Macrophages:  NoNot specified
Hirbod, 2010 [17] 33 subjects, 18-24 years from  Kisumu, Kenya Foreskins obtained from the randomised controlled trial in Kenya [3]. All men were negative for STI for a period of 3 months prior circumcision.   LCs:   150 cells/mm2 in both epidermis and dermis (60% in epidermis and 40% in dermis). Intraepithelial LCs localised as close as 24µm to the outer surface of IFS.   CD4+ T cells:  Abundant CD4+ cells present in dermisγ under the epidermis of foreskin function as early sites of viral replication.   Macrophages:  Exclusively found in dermisγ.
Ganor, 2010 [22] Subjectsy (number of subjects not specified) 17-87years from  Paris, France Personal reasons or phimosis Foreskins with history of infectious pathologies were not used. LCs:  IFS ≈ 580 cells/mmup>2, OFS ≈ 220 cells/mm2, and LC cells only found in epidermis of IFS. IFS >OFS   CD4+ T cells: mainly in dermis, and about 2× concentration in IFS vs. OFS. IFS >OFS                                                                                IFS                  OFS % CCR5 expressing LCs out of total LCs            20.9±  1.6        6.1± 3.1 % CCR5 expressing T cells out of total T cells    35.5± 11.4       5.3± 3.6  Macrophages:   Exclusively found in dermis and the density in IFS=OFSγ.

(IFS, inner foreskin; OFS, outer foreskin; LC, Langerhans cells; STI, sexually transmitted infection; UTI, urinary tract infection).

ϕage range not specified     Ψ number of subjects not specified    *percentages were based on the number of brown staining cells indicating a specific immunophenotypic marker divided by the total number of nucleated cells     †The mean cell percentages were derived from the amount of cellular area staining positive per total cellular area in 5 fields covering the IFS containing 50%epithelium and 50%dermis within each field.    γPrimary data not given.