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Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T-cell responses and expression of immunosuppressive markers.
American Journal of Reproductive Immunology ( IF 2.5 ) Pub Date : 2019-12-06 , DOI: 10.1111/aji.13210
Allen Matubu 1 , Sharon L Hillier 2, 3 , Leslie A Meyn 2 , Kevin A Stoner 3 , Felix Mhlanga 1 , Mike Mbizvo 1 , Aaron Maramba 4 , Zvavahera M Chirenje 1 , Sharon L Achilles 2, 3
Affiliation  

PROBLEM Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En). METHOD OF STUDY Peripheral blood mononuclear cells collected from women aged 18-34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net-En (n = 36) and from women initiating copper intrauterine device (CU-IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4). RESULTS Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD-1+ (P < .001) and CD8+PD-1+ (P < .001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net-En initiation (P < .001 and P < .001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD-1+ (P = .083) and CD8+PD-1+ (P = .936) compared to baseline. CONCLUSION Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.

中文翻译:

醋酸甲羟孕酮和炔诺酮庚酸酯的贮藏库差异影响T细胞反应和免疫抑制标志物的表达。

问题注射避孕药的使用可能会影响免疫细胞的反应性和感染敏感性。我们测量了开始使用醋酸甲羟孕酮(DMPA)或炔诺酮庚酸酯(Net-En)前后妇女的T细胞的反应能力。研究方法:从DMPA(n = 30)或Net-En(n = 36)启动前的18-34岁女性,稳定状态和最低浓度以及启动铜宫内避孕器的女性收集的外周血单核细胞( CU-IUD; n = 32)用佛波醇肉豆蔻酸酯乙酸盐刺激,并使用流式细胞仪进行分析。我们评估了表达程序性细胞死亡1(PD-1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)的T细胞的百分比变化。结果与基线相比,CD4 + CTLA4 +(P <.001)和CD8 + CTLA4 +(P < .01)离体刺激后的T细胞在稳态DMPA浓度下攻击,在最低浓度下无差异(分别为P = .781和P = .463)。在Net-En用户中,在稳态(P = .087)和最低浓度(P = .217)下,未观察到CD4 + CTLA4 + T细胞的差异。DMPA用户在最低浓度时具有较少的CD4 + PD-1 +(P <.001)和CD8 + PD-1 +(P <.001)T细胞。在Net-En启动后,在稳态浓度(分别为P = .002和P = .001)和最低浓度下,CD4 + PD-1 +和CD8 + PD-1 + T细胞的数量减少(P <.001和P <.001)。在CU-IUD用户中,CD4 + CTLA4 +(P = .426)和CD8 + CTLA4 +(P = .169)的数量没有变化,而CD4 + PD-1 +(P = .083)和CD8的数量没有变化。与基线相比,+ PD-1 +(P = .936)。
更新日期:2019-11-01
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