PMID- 34584206
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20211221
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 4
IP  - 1
DP  - 2021 Sep 28
TI  - Regulation of the immune tolerance system determines the susceptibility to 
      HLA-mediated abacavir-induced skin toxicity.
PG  - 1137
LID - 10.1038/s42003-021-02657-2 [doi]
LID - 1137
AB  - Idiosyncratic drug toxicity (IDT) associated with specific human leukocyte 
      antigen (HLA) allotype is a rare and unpredictable life-threatening adverse drug 
      reaction for which prospective mechanistic studies in humans are difficult. Here, 
      we show the importance of immune tolerance for IDT onset and determine whether it 
      is susceptible to a common IDT, HLA-B*57:01-mediated abacavir (ABC)-induced 
      hypersensitivity (AHS), using CD4(+) T cell-depleted programmed death-1 receptor 
      (PD-1)-deficient HLA-B*57:01 transgenic mice (B*57:01-Tg/PD-1(-/-)). Although AHS 
      is not observed in B*57:01-Tg mice, ABC treatment increases the proportion of 
      cytokine- and cytolytic granule-secreting effector memory CD8(+) T cells in 
      CD4(+) T cell-depleted B*57:01-Tg/PD-1(-/-) mice, thereby inducing skin toxicity 
      with CD8(+) T cell infiltration, mimicking AHS. Our results demonstrate that 
      individual differences in the immune tolerance system, including PD-1(high)CD8(+) 
      T cells and regulatory CD4(+) T cells, may affect the susceptibility of humans to 
      HLA-mediated IDT in humans.
CI  - (c) 2021. The Author(s).
FAU - Susukida, Takeshi
AU  - Susukida T
AUID- ORCID: 0000-0003-1512-0753
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Chiba, Japan.
AD  - Laboratory of Cancer Biology and Immunology, Section of Host Defences, Institute 
      of Natural Medicine, University of Toyama, Toyama, Japan.
FAU - Kuwahara, Saki
AU  - Kuwahara S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Chiba, Japan.
FAU - Song, Binbin
AU  - Song B
AD  - Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of 
      Education, School of Pharmacy, Minzu University of China, 100081, Beijing, China.
FAU - Kazaoka, Akira
AU  - Kazaoka A
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Chiba, Japan.
FAU - Aoki, Shigeki
AU  - Aoki S
AUID- ORCID: 0000-0003-2821-0651
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Chiba, Japan. aokishigeki@chiba-u.jp.
FAU - Ito, Kousei
AU  - Ito K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210928
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (Dideoxynucleosides)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Animals
MH  - Dideoxynucleosides/*administration & dosage
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Immune Tolerance/*genetics
MH  - Mice
MH  - Mice, Transgenic
PMC - PMC8479119
COIS- The authors declare no competing interests.
EDAT- 2021/09/30 06:00
MHDA- 2021/12/22 06:00
PMCR- 2021/09/28
CRDT- 2021/09/29 06:45
PHST- 2020/11/19 00:00 [received]
PHST- 2021/09/10 00:00 [accepted]
PHST- 2021/09/29 06:45 [entrez]
PHST- 2021/09/30 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/09/28 00:00 [pmc-release]
AID - 10.1038/s42003-021-02657-2 [pii]
AID - 2657 [pii]
AID - 10.1038/s42003-021-02657-2 [doi]
PST - epublish
SO  - Commun Biol. 2021 Sep 28;4(1):1137. doi: 10.1038/s42003-021-02657-2.