Manfredi A A, Heltai S, Rovere P, Sciorati C, Paolucci C, Galati G, Rugarli C, Vaiani R, Clementi E, Ferrarini M
Laboratory of Tumor Immunology, Scientific Institute HS. Raffaele, Milan, Italy.
Eur J Immunol. 1998 Jun;28(6):1798-806. doi: 10.1002/(SICI)1521-4141(199806)28:06<1798::AID-IMMU1798>3.0.CO;2-E.
Vgamma9/Vdelta2+ T cells specifically recognize Mycobacterium tuberculosis in vitro and are precociously recruited in early mycobacterial lesions. Even if gammadelta T cells are only fortuitously detected in granulomas or bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in shaping the mature alphabeta T cell response against M. tuberculosis is substantiated. Here we provide a molecular explanation for this paradox: the engagement of the gammadelta TCR by mycobacterial antigens induced the expression of CD95 ligand (CD95L) by chronically activated CD95+/CD95L- gammadelta T lymphocytes. The receptor was functional, as CD95/CD95L interaction triggered the bystander death of CD95+ cells by apoptosis. Cell death was abolished by CD95-blocking antibodies. The transient accumulation at the site of infection of CD95L+ gammadelta lymphocytes, capable of interacting with CD95+ leukocytes attracted by the response towards the pathogen, may determine the characteristics of the ensuing granulomatous disease.
Vγ9/Vδ2 + T细胞在体外能特异性识别结核分枝杆菌，并在早期分枝杆菌病变中被过早募集。即使在活动性肺结核患者的肉芽肿或支气管肺泡灌洗中只是偶然检测到γδ T细胞，但它们在塑造针对结核分枝杆菌的成熟αβ T细胞反应中所起的作用已得到证实。在此，我们为这一矛盾现象提供了一种分子解释：分枝杆菌抗原与γδ TCR的结合诱导了慢性活化的CD95 + /CD95L - γδ T淋巴细胞表达CD95配体（CD95L）。该受体具有功能，因为CD95/CD95L相互作用通过凋亡触发了CD95 +细胞的旁观者死亡。CD95阻断抗体可消除细胞死亡。CD95L + γδ淋巴细胞在感染部位的短暂积累，能够与因对病原体的反应而被吸引的CD95 +白细胞相互作用，这可能决定随后肉芽肿疾病的特征。
