Project/Area Number |
13470175
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
|
Research Institution | Kyorin University |
Principal Investigator |
SHIOHARA Tetsuo Kyorin University, School of Medicine, Professor, 医学部, 教授 (10118953)
|
Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Jun Kyorin University, School of Medicine, Assistant, 医学部, 助手 (30255393)
MIZUKAWA Yoshiko Kyorin University, School of Medicine, Assistant, 医学部, 助手 (50301479)
TERAKI Yuichi Kyorin University, School of Medicine, Lecturer, 医学部, 講師 (10188667)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥8,200,000 (Direct Cost: ¥8,200,000)
|
Keywords | Innate immunity / fixed drug eruiption / intraepidermal T cells / NK cells / IL-15 / granzyme B / perforin / innate immunity / granzyme B / perforin / requlatory T細胞 / innate immune cells / 表面内T細胞 / IFN-γ / CD69 / fucosyltransferase VII / CLA |
Research Abstract |
In this study, we asked whether intraepidermal T cells abundantly detected in the resting lesions of fixed drug eruption could display phenotypic properties and functions analogous to innate immune cells, such as NK cells. We found that these T cells were composed of a phenotypically homogeneous population that expresses TCRαβ, CD3, CD8, CD45RA, CD11b, but not CD27 and CD56. This phenotype most closely resembled that of effector memory T cells. Upon stimulation with the causative drug in situ, NKG2D and CD57, frequently expressed on NK cells, were induced to be expressed on some of these intraepidermal T cells. In situ PCR study demonstrated a strong and exclusive induction of IFN-γ mRNA and protein in these T cells with much faster kinetics than their dermal and blood counterparts, upon stimulation in situ. These T cells were also found to have the capacity to kill surrounding keratinocytes through the release of cytotoxic granules, perforin and granzyme B. Thus, these T cells originally evolved to protect tissue integrity can exert an opposite action that is deleterious to the host, when activated in an enhanced or uncontrolled fashion. The activity of these potentially dangerous T cells is therefore carefully controlled to prevent unwanted tissue injury under physiological conditions.
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