Mucosal Immunology Unit, Kings College London, Guy's Hospital, London, United Kingdom.
PLoS One. 2009 Nov 23;4(11):e7938. 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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
流行病学研究表明，同种异体免疫可能抑制母婴 HIV-1 传播，且在多产妇女中比单产妇女中发生频率较低。同种异体免疫反应也可能在无保护的异性性行为中引发，这种性行为与体外对 HIV 感染的抵抗力有关。
方法/主要发现：本研究在明确的异性恋和同性恋一夫一妻制伴侣中进行，他们进行无保护的性行为，以及一个异性恋队列进行有保护的性行为。使用 CFSE 方法，用供体照射的单核细胞刺激 PBMC，以激发同种异体 CD4(+)和 CD8(+)T 细胞增殖反应，并与 3(rd)无关供体单核细胞进行比较。与 3(rd)无关供体单核细胞相比，发现 CD4(+)和 CD8(+)T 细胞对供体照射的单核细胞的同种异体增殖反应显著增加(p<or=0.001)。然而，在异性恋和同性恋伴侣中，与 3(rd)无关供体单核细胞相比，对供体的增殖反应，特别是 CD8(+)T 细胞的增殖反应显著下降，这与耐受有关(p<0.01)。通过流式细胞术检查 CD4(+)CD25(+)FoxP3(+)调节性 T 细胞，发现进行无保护性行为的同性恋伴侣中这些细胞的比例显著高于异性恋伴侣(p<0.05)。体外研究 HIV-1 对 PBMC 的感染性，发现进行无保护性行为的异性恋受试者的 PBMC 感染性明显低于进行有保护性行为的受试者(p=0.02)。
结论/意义：进行无保护性行为的异性恋和同性恋一夫一妻制伴侣对供体的不匹配细胞产生同种异体 CD4(+)和 CD8(+)T 细胞增殖反应，少数可能耐受。然而，同性恋伴侣中 CD4(+)CD25FoxP3(+)调节性 T 细胞的比例较高。除了在进行无保护性行为的异性恋伴侣中发现体外 HIV-1 感染性抑制作用明显大于进行有保护性行为的伴侣外，这些结果表明同种异体免疫可能在 HIV-1 感染的免疫发病机制中发挥重要作用。
