Analysis of Skin-Resident Memory T Cells Following Drug Hypersensitivity Reactions

doi:10.1016/j.jid.2019.11.020

. 2020 Jul;140(7):1442-1445.e4.

doi: 10.1016/j.jid.2019.11.020. Epub 2019 Dec 26.

Analysis of Skin-Resident Memory T Cells Following Drug Hypersensitivity Reactions

Affiliations

¹ Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Infectious Diseases, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia. Electronic address: Jason.TRUBIANO@austin.org.au.
² Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
³ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
⁴ Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia.
⁵ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Dermatology, Austin Health, Heidelberg, Victoria, Australia.
⁷ Department of Dermatology, Vanderbilt University Medical Centre, Nashville, TN, USA.
⁸ Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, TN, USA; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁹ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. Electronic address: lkmackay@unimelb.edu.au.

PMID: 31883960
PMCID: PMC7369252
DOI: 10.1016/j.jid.2019.11.020

Analysis of Skin-Resident Memory T Cells Following Drug Hypersensitivity Reactions

Jason A Trubiano et al. J Invest Dermatol. 2020 Jul.

. 2020 Jul;140(7):1442-1445.e4.

doi: 10.1016/j.jid.2019.11.020. Epub 2019 Dec 26.

Authors

Affiliations

¹ Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Infectious Diseases, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia; The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia. Electronic address: Jason.TRUBIANO@austin.org.au.
² Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
³ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
⁴ Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia.
⁵ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Dermatology, Austin Health, Heidelberg, Victoria, Australia.
⁷ Department of Dermatology, Vanderbilt University Medical Centre, Nashville, TN, USA.
⁸ Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, TN, USA; Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁹ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. Electronic address: lkmackay@unimelb.edu.au.

PMID: 31883960
PMCID: PMC7369252
DOI: 10.1016/j.jid.2019.11.020

No abstract available

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Conflict of interest statement

Conflict of Interest Statement:

The authors state no conflict of interest

Figures

**Figure 1.**
T_RM cell persistence in skin following intradermal drug inoculation in patients with a history of DRESS or MPE. IDT with causative drugs was performed on five patients (3 DRESS [circles] and 2 MPE [squares]), and skin biopsies were taken from the reactive exanthema (Lesion) and control (Ctrl) skin 1 day (Acute-IDT) and > 8 weeks (Post-IDT, red) later. Both MPE patients had CLL. (a) Image shows Lesion and Ctrl skin biopsy sites during acute-IDT reaction and post-IDT from a representative patient (ID 1). The site of the control biopsy was distinct from the adjacent lesion. This patient was IDT positive to additional beta-lactam antibiotics (benzylpenicillin, ampicillin), which are routinely tested in the setting of a primary beta-lactam allergy (flucloxacillin). Patient consent for image publication was obtained. (b–e) Flow cytometry was performed on lymphocytes extracted from skin biopsies. Individual data points are shown (n = 5) and paired samples connected where available (n = 3). (b) Representative flow cytometry plots show CD4 and CD8 staining of CD3⁺CD45RO⁺ T cells. The mean frequency is shown (n = 4 Acute-IDT, n = 4 Post-IDT). (c) Ratio of the number of CD4⁺ (left) and CD8⁺ (right) T cells isolated from Lesion compared with Ctrl skin. (d) Representative flow cytometry plots show CD69 and CD103 expression by CD4⁺ (left) and CD8⁺ (right) CD3⁺CD45RO⁺ T cells. The mean frequency is shown (n = 5). (e) Ratio of the number of CD103⁻ or CD103⁺ T cells isolated from Lesion compared with Ctrl skin of CD69⁺ CD4⁺ T cells (left) and CD69+ CD8⁺ T cells (right). CLL, chronic lymphocytic leukemia; Crtl, control; DRESS, drug reaction with eosinophilia and systemic symptoms; IDT, intradermal drug testing; Lesion, reactive exanthema; MPE, maculopapular exanthema; T_RM, tissue-resident memory T cells.

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References

1. Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011;89(6):806–15. - PubMed
1. Gamradt P, Laoubi L, Nosbaum A, Mutez V, Lenief V, Grande S, et al. Inhibitory checkpoint receptors control CD8(+) resident memory T cells to prevent skin allergy. J Allergy Clin Immunol 2019;143(6):2147–57 e9. - PubMed
1. Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol 2009;10(5):524–30. - PubMed
1. Iriki H, Adachi T, Mori M, Tanese K, Funakoshi T, Karigane D, et al. Toxic epidermal necrolysis in the absence of circulating T cells: a possible role for resident memory T cells. J Am Acad Dermatol 2014;71(5):e214–6. - PubMed
1. Klicznik MM, Morawski PA, Hollbacher B, Varkhande S, Motley S, Kuri-Cervantes L, et al. Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects. bioRxiv 2019;361758. - PMC - PubMed

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[1] Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011;89(6):806–15. - PubMed

[2] Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011;89(6):806–15. - PubMed

[3] Gamradt P, Laoubi L, Nosbaum A, Mutez V, Lenief V, Grande S, et al. Inhibitory checkpoint receptors control CD8(+) resident memory T cells to prevent skin allergy. J Allergy Clin Immunol 2019;143(6):2147–57 e9. - PubMed

[4] Gamradt P, Laoubi L, Nosbaum A, Mutez V, Lenief V, Grande S, et al. Inhibitory checkpoint receptors control CD8(+) resident memory T cells to prevent skin allergy. J Allergy Clin Immunol 2019;143(6):2147–57 e9. - PubMed

[5] Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol 2009;10(5):524–30. - PubMed

[6] Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol 2009;10(5):524–30. - PubMed

[7] Iriki H, Adachi T, Mori M, Tanese K, Funakoshi T, Karigane D, et al. Toxic epidermal necrolysis in the absence of circulating T cells: a possible role for resident memory T cells. J Am Acad Dermatol 2014;71(5):e214–6. - PubMed

[8] Iriki H, Adachi T, Mori M, Tanese K, Funakoshi T, Karigane D, et al. Toxic epidermal necrolysis in the absence of circulating T cells: a possible role for resident memory T cells. J Am Acad Dermatol 2014;71(5):e214–6. - PubMed

[9] Klicznik MM, Morawski PA, Hollbacher B, Varkhande S, Motley S, Kuri-Cervantes L, et al. Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects. bioRxiv 2019;361758. - PMC - PubMed

[10] Klicznik MM, Morawski PA, Hollbacher B, Varkhande S, Motley S, Kuri-Cervantes L, et al. Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects. bioRxiv 2019;361758. - PMC - PubMed

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Analysis of Skin-Resident Memory T Cells Following Drug Hypersensitivity Reactions

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Analysis of Skin-Resident Memory T Cells Following Drug Hypersensitivity Reactions

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