Laura K. Mackay, et al.
Science, 2016
Tissue-resident memory T (Trm) cells provide immediate protection against microbial invaders. In this paper, the authors reported Hobit and Blimp1 both instructed tissue retention of diverse tissue-resident lymphocyte populations in skin, gut, liver, and kidney in mice. First, they found that Hobit and Blimp1 had different expression after virus infection and demonstrated that Hobit was specifically required for Trm cell development and Blimp1 collaborated with Hobit in a synergistic manner. Then, focusing on innate tissue-resident lymphocytes, they found Hobit and Blimp1 were not required for migration but for maintenance of liver-resident NKT and NK cells. next, they performed genome-wide transcriptional profiling to identify 30 genes, whose expression pattern was specifically associated with tissue residency independent of lineage or tissue of origin. Especially, Hobit was the only transcription factor specifically up-regulated in tissue-resident lymphocytes. Finally, they performed chromatin immunoprecipitation (ChIP) sequencing using CD8+ T cells expressing biotin-tagged Blimp1 or V5-tagged Hobit. It demonstrates that Hobit and Blimp1 mediate a transcriptional program of tissue residency that is shared among Trm, trNK, and NKT cells and includes the suppression of tissue egress genes.https://science.sciencemag.org/content/352/6284/459.long
Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses
Felix M. Behr, Loreto Parga-Vidal, et al.
Nature Immunology, 2020
Little is known regarding the contribution of tissue-resident memory CD8+ T cells (TRM cells) to secondary responses beyond their local tissue. In this paper, the authors utilized a unique lineage tracer mouse model exploiting Hobit to fate map the TRM progeny in secondary responses. First, they developed Hobit reporter mice containing a reporter cassette encoding for the fluorescent protein tdTomato, the Cre recombinase, and the diphtheria toxin receptor (DTR) in the Hobit locus. Hobit reporter mice were crossed with T cell receptor (TCR) transgenic OT-I mice to enable the study of antigen-specific T cell responses developing. The tdTomato expression in Hobit reporter mice specifically identified TRM cells arising in the liver and small intestine after oral Lm-OVA infection. Then, they found that reinfection at intestinal sites drives the local expansion of TRM cells and the emergence of TRM cells in draining lymph nodes. Next, they generated Hobit lineage tracer mice by crossing Hobit reporter OT-I mice with ROSA26-flox-stop-flox-eYFP (ROSA26-eYFP) mice. The findings conclude that Hobit+ TRM cells generated considerable populations of secondary effector and memory T cells in the circulation, which downregulated Hobit expression in response to antigen recognition. Further, the proportion of TRM cells that downregulate Hobit expression after rechallenge do not appear to persist as secondary TRM cells, exhibit limited ability to form TCM cells, and mainly generate KLRG1+CX3CR1+ TEM cells. Secondary ex-Hobit+ T cells constitute a transcriptionally and functionally distinct effector memory subset with enhanced capacity to protect against reinfection. So CD8+ TRM cells substantially contribute to secondary memory responses after pathogen rechallenge.
https://www.nature.com/articles/s41590-020-0723-4