Heterosexual and Homosexual Partners Practising Unprotected Sex May Develop Allogeneic Immunity and to a Lesser Extent Tolerance

• Published in: PloS one Vol. 4; no. 11; p. e7938
• Main Authors: Kingsley, Cherry, Peters, Barry, Babaahmady, Kaboutar, Pomeroy, Laura, Rahman, Durdana, Vaughan, Robert, Lehner, Thomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.11.2009; Public Library of Science (PLoS)
• Subjects: Adult; B cells; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chemokines; Cohort Studies; Comparative analysis; Cytometry; Dendritic cells; Disease transmission; Epidemiology; Female; Flow cytometry; Forkhead Transcription Factors - metabolism; Foxp3 protein; Heterosexuality; HIV; HIV infections; HIV Infections - immunology; Homosexuality; Hospitals; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune System; Immune Tolerance - immunology; Immunity; Immunological tolerance; Immunology; Immunology/Immune Response; Immunology/Innate Immunity; Immunoregulation; Infections; Infectious diseases; Infectious Diseases/HIV Infection and AIDS; Infectivity; Inhibition; Interleukin-2 Receptor alpha Subunit - biosynthesis; Leukocytes, Mononuclear - cytology; Lymphocytes; Lymphocytes T; Male; Monocytes; Pathogenesis; Peripheral blood mononuclear cells; Preeclampsia; Sex; Sex industry; Sexually transmitted diseases; STD; T cell receptors; T cells; Transplants & implants; Unsafe Sex; United Kingdom > UK
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007938

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. 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). 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.