研究発表を行った学会；国際免疫学会
２００４年７月１８日〜２３日（カナダ　モントリオール）
[Title of abstract]The role of CXCR1/IL-8 in acquired immunity: CXCR1 expression on effector CD8+ T cells

[Authors]
Hiroshi Takata1, Hiroko Tomiyama1, Mamoru Fujiwara1, Naoki Kobayashi1, 2 and Masafumi Takiguchi1

[Institution]
1Division of Viral immunology, Center for AIDS Research, Kumamoto University, Japan
2Department of Pediatrics, School of Medicine, Yokohama City University, Japan

[Background]
IL-8 is a potent inflammatory cytokine that induces chemotaxis of neutrophils expressing IL-8 receptors CXCR1/2. This suggests that CXCR1/2-IL-8 plays an important role in bacterial elimination. However, the role of CXCR1/2-IL-8 in viral eradication remains unknown. Therefore, we investigated the CXCR1/2 expression on CD8+ T cells to clarify the role of CXCR1/2-IL-8 in viral infection.

[Methods]
PBMCs from peripheral blood of healthy individuals were stained using anti-CXCR1/2, anti-CD8, anti-CD27, anti-CD28, anti-CD45RA and anti-perforin mAbs and/or tetrameric HLA class I-EBV- or HCMV-peptide complexes. Those cells were analyzed using flow cytometry. Cytotoxic activity of CXCR1+ CD8+ T cells for target cells pulsed with HCMV-1 epitope peptide was assessed by a standard 51Cr-release assay. The effect of IL-8 on chemotactic activity of CD8+ T cells was tested.

[Results]
CD3+CD8+ cells did not express CXCR2 but partially expressed CXCR1. CXCR1+ cells were predominantly found among CD8+ T cells having effector phenotype, CD27-/lowCD28-CD45RA+/- or CD27-CD28-CD45RA+/-. These results suggest that CXCR1 is expressed on effector and memory/effector CD8+ T cells. Indeed, CXCR1 expression was positively correlated to perforin expression. Six-color flowcytometric analysis using the tetramers demonstrated that HCMV-specific CD8+ T cells, which mostly express the effector and memory/effector phenotype and have cytolytic function, expressed CXCR1 while EBV-specific CD8+ T cells, which mostly express the memory phenotype and have no cytolytic function, did not express this receptor. CXCR1+ CD8+ T cells killed HCMV epitope peptide-pulsed cells more effectively than total CD8+ T cells. The results of a chemotaxis assay showed that the migration of CXCR1+CD8+ T cells was induced by IL-8.

[Conclusion]
We showed specific expression and function of CXCR1 on effector and memory/effector CD8+ T cells. This suggests that the IL8-CXCR1 pathway may play an important role in homing of effector CD8+ T cells in viral infection.