Abstract:
:Naïve phenotype (NP) T cells spontaneously initiate homeostatic proliferation (HP) as T-cell output is reduced because of physiologic thymic involution with age. However, the effects of sustained HP on overall immune function are poorly understood. We demonstrated that the NP CD8+ T cell population in adult thymectomized mice showing accelerated HP has an increased capacity for TCR-mediated interferon-γ and tumor necrosis factor α production, which is attributed to an increase in CXCR3+ cells in the NP CD8+ T cell population. The CXCR3+ NP CD8+ T cells developed during persistent HP with a slow cell division rate, but rarely during robust antigen-driven proliferation with a fast cell division rate. In ontogeny, the proportions of CXCR3+ cells in the NP CD8+ T cell population showed a biphasic profile, which was high at the newborn and aged stages. Upon transfer, CXCR3+ NP CD8+ T cells, but not CXCR3- NP CD8+ T cells, potently enhanced Th17-mediated inflammatory tissue reactions in vivo. Furthermore, CXCR3high NP CD8+ T cells with similar features were also detected at variable levels in healthy human blood. These results suggest that CXCR3+ NP CD8+ T cells generated during physiological HP significantly impact overall immunity at the immunologically vulnerable neonatal and aged stages.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Kato A,Takaori-Kondo A,Minato N,Hamazaki Ydoi
10.1002/eji.201747431subject
Has Abstractpub_date
2018-10-01 00:00:00pages
1663-1678issue
10eissn
0014-2980issn
1521-4141journal_volume
48pub_type
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