TCF1 and Tox define different subsets of CD4 T cells in patients with Sézary syndrome.
TCF1 and Tox define different subsets of CD4 T cells in patients with Sézary syndrome.
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TCF1 和 Tox 定义了 Sézary 综合征患者 CD4 T 细胞的不同亚群。
DOI：
10.1080/10428194.2022.2081326
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发表时间：
2022
影响因子：
2.6
通讯作者：
Rook,AlainH
中科院分区：
文献类型：
--
作者：
Wysocka,Maria;Jariwala,Neha;Zhang,Kevin;Benoit,Bernice;Rook,AlainH
Sézary syndrome (SS), a leukemic form of cutaneous T cell lymphoma (CTCL), is a rare T-cell malignancy which is defined by circulating malignant CD4 þ CD26 À T cells [1]. It is characterized by severely impaired immune responses and elevated expression of several inhibitory molecules, including PD1, TIGIT, and the transcription factor Tox that has been implicated in the malignant transformation of the CTCL [2-5]. Tox, critical in establishing the CD4 T cell lineage, has been considered a marker for terminally exhausted cells and is often co-expressed with the aforementioned inhibitory receptors [6-8]. Recently Sekine et al. demonstrated the expression of Tox on activated T cells from healthy donors along with the transcription factor, T cell factor 1 (TCF1), challenging the notion that Tox is exclusively an exhaustion marker [9]. TCF1 identifies the population of T cells which self-renew and generate immune responses during checkpoint blockade targeting PD1 [10-12]. The high frequency of TCF1 expressing T cells within tumors correlated with favorable clinical outcomes [13, 14]. We investigated the expression of TCF1 and Tox on CD4 T cells from SS patients and healthy donors by flow cytometry. Patients (n¼ 21) with erythroderma and circulating malignant T cells were diagnosed as defined by Olsen et al.; B2 patients were stage IVA while B0-B1 patients were stage IA-IIIA [15]. The following groups of patients were selected for studies:(1) patients diagnosed with advanced-stage IVA and defined by flow cytometry as having a circulating single dominant TCRVb clone (n¼ 7),(2) patients diagnosed with stage IVA but with no defined TCRVb (n¼7),(3) patients defined originally with stage IVA but currently in complete remission (CR, n¼ 3), and four patients diagnosed with less advanced stages IB, IIB, and IIIA. PBMC from patients with no prior treatments were used in the studies except for samples from 3 patients in complete remission whose original samples were no longer available. PBMC samples from agematched healthy donors (HD, n¼ 6) were provided by the Immunology Core of the University of Pennsylvania. Figure 1 (A) shows populations of CD4 T cells expressing TCF1 and/or Tox from a representative healthy donor (HD, upper panel) and patient (lower panel). TCF1 and Tox identified three CD4 T cell populations: TCF1+ Tox À, TCF1+ Tox+, and TCF1 À Tox+ among SS patients and HD (Figure 1 (A)). The preliminary data revealed that the percentage of patientsL CD4 T cells expressing TCF1 was significantly lower compared to CD4 T cells from HD (SS patients, 51.2% versus HD, 77.3%). Tox expression was not significantly different between patients and HD. More detailed analysis showed that the population expressing TCF1 þ Tox À in SS patients with stage IVA and with or without a defined TCRVb, was significantly decreased compared to HD, while the population expressing TCF1 À Tox þ among those patients was significantly increased (Figure 1 (B), left and middle panels) The percentage of TCF1 þ Tox þ CD4 T cells was also significantly lower in stage IVA patients with a dominant TCRVb (Figure 1 (B), middle panel). There were no significant differences in frequencies of the aforementioned populations between HD and patients diagnosed with stage IA-IIIA disease or those in clinical remission (Figure 1 (B), right panel). Further studies were focused on patients diagnosed with stage IVA and addressed the expression of CD26, PD1, TIGIT, and TCRVb in association with TCF1 þ and/or Tox þ expression on CD4 populations. The populations expressing single TCF1 þ from HD and patients consisted of the highest percentage of cells …
