Characterization of lung γδ T cells following intranasal infection with Mycobacterium bovis bacillus Calmette-Guerin

被引:86
|
作者
Dieli, F
Ivanyi, J
Marsh, P
Williams, A
Naylor, I
Sireci, G
Caccamo, N
Di Sano, C
Salerno, A
机构
[1] Univ Palermo, Dipartimento Biopatol, I-90134 Palermo, Italy
[2] Kings Coll London, Guys Dent & Med Sch, London WC2R 2LS, England
[3] Ctr Appl Microbiol & Res, Salisbury, Wilts, England
[4] CNR, Inst Adv Diagnost Methodol, Palermo, Italy
来源
JOURNAL OF IMMUNOLOGY | 2003年 / 170卷 / 01期
关键词
D O I
10.4049/jimmunol.170.1.463
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lungs are considered to have an impaired capacity to contain infection by pathogenic mycobacteria, even in the presence of effective systemic immunity. In an attempt to understand the underlying cellular mechanisms, we characterized the gammadelta T cell population following intranasal infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG). The peak of gammadelta T cell expansion at 7 days postinfection preceded the 30 day peak of alphabeta T cell expansion and bacterial count. The expanded population of gammadelta T cells in the lungs of BCG-infected mice represents an expansion of the resident Vgamma2 T cell subset as well as an influx of Vgamma1 and of four different V5 gene-bearing T cell subsets. The gammadelta T cells in the lungs of BCG-infected mice secreted IFN-gamma following in vitro stimulation with ionomycin and PMA and were cytotoxic against BCG-infected peritoneal macrophages as well as against the uninfected J774 macrophage cell line. The cytotoxicity was selectively blocked by anti-gammadelta TCR mAb and strontium ions, suggesting a granule-exocytosis killing pathway. Depletion of gammadelta T cells by injection of specific mAb had no effect on the subsequent developing CD4 T cell response in the lungs of BCG-infected mice, but significantly reduced cytotoxic activity and IFN-gamma production by lung CD8 T cells. Thus, gammadelta T cells in the lungs might help to control mycobacterial infection in the period between innate and classical adaptive immunity and may also play an important regulatory role in the subsequent onset of alphabeta T lymphocytes.
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页码:463 / 469
页数:7
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