2004 Fiscal Year Final Research Report Summary
Functions and roles of pathogenic T cells in drug hypersensitivity
| Project/Area Number |
15591173
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
HASHIZUME Hideo Hamamatsu University School of Medicine, Dermatology, Associate Professor, 医学部, 助教授 (50237921)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIGAWA Masahiro Hamamatsu University School of Medicine, Dermatology, Professor, 医学部, 教授 (80115873)
YAGI Hiroaki Hamamatsu University School of Medicine, Dermatology, Assistant Professor, 医学部附属病院, 講師 (20242779)
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| Project Period (FY) |
2003 – 2004
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| Keywords | T cell / drug allergy / cytokine / herpesvirus / chemokine |
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| Research Abstract |
We investigated immunologically on the circulating lymphocytes from patients with drug-induced eruption including drug-induced hypersensitivity (DIHS) and acute generalized exanthematous pustulosis (AGEP). We experienced three cases of drug-induced hypersensitivity syndrome (DINS) associated with herpesvirus reactivation and investigation of the immunological characteristics of the circulating and skin-infiltrating lymphocytes. In tribenoside-induced DIHS, activated CD8+ T cells outnumbered CD4+ cells in both the circulation and the skin lesions. Upon in vitro stimulation with the drug, CD4+ cells proliferated and produced interferon-γ. The circulating CD8+ cells used limited T-cell receptor Vβs, some of which are restricted to cytomegalovirus-derived peptide in the context of the HLA-A2 haplotype. CD8+ cells and cytomegalovirus-containing cells closely co-localized in the skin lesions. These results suggested that CD4+ cells were drub reactive, whereas cytomegalovirus activated CD8+ c
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ells in the present case. In the other two cases of DIHS, phenotypes of the circulating lymphocytes similarly changed ; CD4+ cells activated first and CD8+ cells activated later during the course with hervesvirus reactivation at the same time. Therefore, these two cell types seemed to play a distinct role in DIMS.
In three cases of AGEP, we established drug-reactive T cell clones/lines and investigated their function. These clones/lines proliferated in response to the causative drugs (stimulation index>1.5) and expressed CD3 and CD4/CD8 molecules. T-cell receptor Vβs that they used were heterogeneous. All the clones/lines were positive for CXCR-3 which is chemokine receptor for IP-10 produced by keratinocyles. Most of CD4+ clones/lines produced IL-2 and IFNN-γ, indicating to be Th1 cells. Interestingly, they produced large amount of TNF-α and IL-8, which attracts neutrophils. The functions of the pathogenic T cells reflect the clinical presentations manifesting neutrophilic abscesses in AGED. Less
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