title: Heterosexual and homosexual partners practising unprotected sex may develop allogeneic immunity and to a lesser extent tolerance.
abstract: BACKGROUND
  Epidemiological studies suggest that allogeneic immunity may inhibit HIV-1 transmission from mother to baby and is less frequent in multiparous than uniparous women. Alloimmune responses may also be elicited during unprotected heterosexual intercourse, which is associated ex vivo with resistance to HIV infection.
  
  
  RESULTS
  The investigation was carried out in well-defined heterosexual and homosexual monogamous partners, practising unprotected sex and a heterosexual cohort practising protected sex. Allogeneic CD4(+) and CD8(+) T cell proliferative responses were elicited by stimulating PBMC with the partners' irradiated monocytes and compared with 3(rd) party unrelated monocytes, using the CFSE method. Significant increase in allogeneic proliferative responses was found in the CD4(+) and CD8(+) T cells to the partners' irradiated monocytes, as compared with 3(rd) party unrelated monocytes (p<or=0.001). However, a significant decrease in proliferative responses, especially of CD8(+) T cells to the partners' compared with 3(rd) party monocytes was consistent with tolerization, in both the heterosexual and homosexual partners (p<0.01). Examination of CD4(+)CD25(+)FoxP3(+) regulatory T cells by flow cytometry revealed a significantly greater proportion of these cells in the homosexual than heterosexual partners practising unprotected sex (p<0.05). Ex vivo studies of infectivity of PBMC with HIV-1 showed significantly greater inhibition of infectivity of PBMC from heterosexual subjects practising unprotected compared with those practising protected sex (p = 0.02).
  
  
  CONCLUSIONS
  Both heterosexual and homosexual monogamous partners practising unprotected sex develop allogeneic CD4(+) and CD8(+) T cell proliferative responses to the partners' unmatched cells and a minority may be tolerized. However, a greater proportion of homosexual rather than heterosexual partners developed CD4(+)CD25FoxP3(+) regulatory T cells. These results, in addition to finding greater inhibition of HIV-1 infectivity in PBMC ex vivo in heterosexual partners practising unprotected, compared with those practising protected sex, suggest that allogeneic immunity may play a significant role in the immuno-pathogenesis of HIV-1 infection.
authors: Mucosal Immunology Unit, Kings College London, Guy's Hospital, London, United Kingdom.
authors: Cherry
authors: C
authors: Kingsley
authors: Barry
authors: B
authors: Peters
authors: Kaboutar
authors: K
authors: Babaahmady
authors: Laura
authors: L
authors: Pomeroy
authors: Durdana
authors: D
authors: Rahman
authors: Robert
authors: R
authors: Vaughan
authors: Thomas
authors: T
authors: Lehner
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D020010:Heterosexuality; D006716:Homosexuality; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D047568:Unsafe Sex
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit