| First Author | Labarthe L | Year | 2019 |
| Journal | J Leukoc Biol | PubMed ID | 31378988 |
| Mgi Jnum | J:278786 | Mgi Id | MGI:6356453 |
| Doi | 10.1002/JLB.5HI1018-410RR | Citation | Labarthe L, et al. (2019) Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF-A2 humanized mice resemble those in human samples. J Leukoc Biol |
| abstractText | This work sought to confirm the human-like expression of exhaustion and senescence markers in a mouse model with a humanized immune system (HIS): the Balb/c Rag2(KO) IL2rgc(KO) Sirpalpha(NOD) Flk2(KO) HLA-A2(HHD) (BRGSF-A2) mouse reconstituted with human CD34(+) cord blood cells. With regard to senescence markers, the percentage of CD57(+) T cells was higher in the bone marrow (BM) than in the spleen or blood. The same was true for KLRG1(+) hCD8(+) T cells. With regard to exhaustion markers, the percentage of programmed death 1 (PD-1(+) ) T cells was higher in the BM than in the spleen or blood; the same was true for TIGIT(+) hCD4(+) cells. These tissue-specific differences were related to both higher proportions of memory T cells in BM and intrinsic differences in expression within the memory fraction. In blood samples from HIS mice and healthy human donors (HDs), we found that the percentage of KLRG1(+) cells among hCD8(+) T cells was lower in HIS compared to HDs. The opposite was true for CD4(+) T cells. Unexpectedly, a high frequency of KLRG1(+) cells was observed among naive T cells in HIS mice. CD57 expression on T cells was similar in blood samples from HIS mice and HDs. Likewise, PD-1 expression was similar in the two systems, although a relatively low proportion of HIS hCD4(+) T cells expressed TIGIT. The BRGSF-A2 HIS mouse's exhaustion and senescence profile was tissue specific and relatively human like; hence, this mouse might be a valuable tool for determining the preclinical efficacy of immunotherapies. |
