美国洛克菲勒大学Daniel Mucida、Angelina M. Bilate等研究人员合作发现，T细胞受体是肠道CD4+上皮内淋巴细胞分化而非维持所必需。这一研究成果于2020年10月5日在线发表在国际学术期刊《免疫》上。
Title: T Cell Receptor Is Required for Differentiation, but Not Maintenance, of Intestinal CD4+ Intraepithelial Lymphocytes
Author: Angelina M. Bilate, Mariya London, Tiago B.R. Castro, Luka Mesin, Juliana Bortolatto, Suppawat Kongthong, Audrey Harnagel, Gabriel D. Victora, Daniel Mucida
Abstract: The gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneousT cell population with cytotoxic and regulatory properties, which can be acquiredat the epithelial layer. However, the role of T cell receptor (TCR) in this processremains unclear. Single-cell transcriptomic analyses revealed distinct clonal expansionsbetween cell states, with CD4+CD8αα+ IELs being one of the least diverse populations. Conditional deletion of TCR on differentiatingCD4+ T cells or of major histocompatibility complex (MHC) class II on intestinal epithelialcells prevented CD4+CD8αα+ IEL differentiation. However, TCR ablation on differentiated CD4+CD8αα+ IELs or long-term cognate antigen withdraw did not affect their maintenance. TCRre-engagement of antigen-specific CD4+CD8αα+ IELs by Listeria monocytogenes did not alter their state but correlated with reduced bacterial invasion. Thus, localantigen recognition is an essential signal for differentiation of CD4+ T cells at the epithelium, yet differentiated IELs are able to preserve an effectorprogram in the absence of TCR signaling.