Department of Microbiology and Immunology, Western University, London, Canada.
Rakai Health Sciences Program, Kalisizo, Uganda.
PLoS One. 2024 Mar 1;19(3):e0297884. doi: 10.1371/journal.pone.0297884. eCollection 2024.
Voluntary medical male circumcision (VMMC) reduces HIV acquisition by at least 60%, but the determinants of HIV susceptibility in foreskin tissues are incompletely understood. Flow cytometry is a powerful tool that helps us understand tissue immune defenses in mucosal tissue like the inner foreskin, but foreskin flow cytometry has only been validated using fresh tissue samples. This restricts immune analyses to timepoints immediately after surgical acquisition and hinders research in this area. We compared fresh analysis with whole tissue cryopreservation and later thawing and digestion to analyze CD4+ T cell populations relevant to HIV susceptibility (CCR5, CD25, CD127, CCR4, CXCR3, CCR6, CCR10, HLA-DR, and CD38). Eight foreskin samples from HIV-negative males aged >18 years were collected after VMMC. For each sample, half the foreskin was immediately cryopreserved for later digestion and flow cytometry analysis, while the remaining tissues were analyzed fresh. We demonstrate no significant impact of cryopreservation on CD4+ T cell expression of CD25, CCR4, CCR6, HLA-DR, CCR10, or CD127. Although expression levels of CCR5, CD38, and CXCR3 were increased after cryopreservation, the relative ranking of participants was retained. In conclusion, cryopreserved foreskin tissues may be suitable for subsequent digestion and flow cytometry phenotyping of HIV-susceptible T cell populations.
自愿男性包皮环切术(VMMC)可降低至少 60%的 HIV 感染风险,但包皮组织中 HIV 易感性的决定因素尚未完全阐明。流式细胞术是一种强大的工具,可以帮助我们了解黏膜组织(如内包皮)中的组织免疫防御,但包皮流式细胞术仅在使用新鲜组织样本时得到验证。这限制了对手术获得后立即发生的时间点的免疫分析,并阻碍了该领域的研究。我们比较了新鲜分析与整个组织冷冻保存以及随后的解冻和消化,以分析与 HIV 易感性相关的 CD4+T 细胞群(CCR5、CD25、CD127、CCR4、CXCR3、CCR6、CCR10、HLA-DR 和 CD38)。在 VMMC 后,从 18 岁以上 HIV 阴性男性中收集了 8 个包皮样本。对于每个样本,一半的包皮立即冷冻保存用于以后的消化和流式细胞术分析,而其余的组织则进行新鲜分析。我们证明冷冻保存对 CD4+T 细胞表达 CD25、CCR4、CCR6、HLA-DR、CCR10 或 CD127 没有显著影响。尽管冷冻保存后 CCR5、CD38 和 CXCR3 的表达水平增加,但参与者的相对排名得以保留。总之,冷冻保存的包皮组织可能适合随后消化和流式细胞术分析 HIV 易感 T 细胞群的表型。