Semen reduces CD4+ T cell susceptibility to HIV infection
E. Balandya1, S. Sheth1, K. Sanders2, W. Wieland-Alter1, T. Lahey1
1Dartmouth Medical School, Lebanon, United States, 2Dartmouth College, Hanover, United States
Background: Semen is the major vehicle of HIV transmission worldwide, but its impact on the primary cellular targets of HIV infection, CD4+ T cells, remains unclear. We examined the impact of semen on CD4+ T cell infection with HIV as well as expression of markers of susceptibility to HIV infection.
Methods: We measured CD4+ T cell infection with HIV after incubation with cell-free seminal plasma (SP) from 20 HIV-negative donors, correlating the percent change in T cell HIV infection with the impact of SP on T cell expression of the HIV receptor CD4, the activation marker CD38, T cell proliferation and semen cytokine levels. Non-parametric analyses were used for statistical comparisons.
Results: SP significantly reduced CD4+ T cell infection by HIV IIIB (47.92% vs. 22.84%, P=0.0014) and HIV BaL (27.55% vs. 1.78%, P=0.0021). Further, SP reduced T cell surface CD4 expression compared to the medium control (mean fluorescence intensity [MFI] 12,430 vs. 7,613, P=0.0003), as well as CD4 mRNA (0.24 fold change, P=0.0070). SP also reduced T cell CD38 expression (MFI 2,936 vs. 2,293, P=0.0003), and T cell proliferation (49.42% vs. 13.44%, P=0.0003). Semen mediated reduction of these markers correlated highly and significantly with the reduction in CD4+ T cell infection with HIV. Importantly, semen levels of the anti-inflammatory cytokine TGFß3 correlated significantly with semen mediated reduction in T cell CD4 expression (Spearman rho [ρ] = 0.5970, P= 0.0055), activation (Spearman ρ = 0.4752, P= 0.0342), proliferation (Spearman ρ = 0.4513, P= 0.0458) and reduction in CD4+ T cell HIV infection (Spearman ρ = 0.5506, P= 0.0097).
Conclusions: Semen reduces CD4+ T cell CD4 expression, activation and proliferation, and protects CD4+ T cells from HIV infection. TGFß3 in semen may be the key protective cytokine. This is a novel finding with the potential to lead to development of novel means of preventing HIV transmission.
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