Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8⁺ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8⁺ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8⁺ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8⁺ T cell numbers at 20 days postinfection. Anti-CD20 injection increased the frequency of apoptotic CD8⁺ T cells, decreased the number of effector and memory CD8⁺ T cells, and reduced the frequency of proliferating and cytokine-producing CD8⁺ T cells. Accordingly, infected anti-CD20-treated mice presented lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8⁺ T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened the CD8⁺ T cell response, when this had already been generated, indicating that B cells were involved in the maintenance rather than the induction of CD8⁺ T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of interleukin-6 (IL-6)- and IL-17A-producing cells, and recombinant IL-17A (rIL-17A) injection partially restored the CD8⁺ T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8⁺ T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly.

中文翻译：

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CD8 + T细胞免疫力受到抗CD20处理的损害，并被白介素17A拯救。

抗CD20的治疗已用于许多B细胞在其中发挥致病作用的疾病，与细胞内感染的易感性有关。在这里，我们使用克氏锥虫感染的实验模型研究了抗CD20注射对CD8 ⁺ T细胞免疫的影响，其中CD8 ⁺ T细胞起着关键作用。在克氏锥虫感染之前，用抗CD20处理C57BL / 6小鼠的B细胞耗竭。受感染的抗CD20处理的小鼠表现出CD8 ⁺ T细胞反应，具有保守的扩增阶段，随后发生早期收缩，从而导致总和寄生虫特异性CD8 ^+的大量减少。感染后20天的T细胞数目。抗CD20注射增加凋亡CD8 ⁺ T细胞的频率，减少效应和记忆CD8 ⁺ T细胞的数量，并减少增殖和产生细胞因子的CD8 ⁺ T细胞的频率。因此，感染的抗CD20治疗的小鼠在体内表现出了对克鲁斯杆菌刺激的靶细胞的较低细胞毒性。CD8 ⁺ T细胞免疫力的所有这些改变都与组织寄生虫增多有关。当已经产生抗CD20的注射后，它也减弱了CD8 ⁺ T细胞的应答，表明B细胞参与了维持而不是诱导CD8。⁺ T细胞免疫力。抗CD20注射还导致白介素6（IL-6）和IL-17A产生细胞的频率显着降低，重组IL-17A（rIL-17A）注射部分恢复了CD8 ⁺ T细胞应答在受感染的抗CD20治疗的小鼠中。因此，抗CD20降低了CD8 ⁺ T细胞的免疫力，而IL-17A是直接或间接挽救缺陷反应的候选药物。