Ueta C, Tsuyuguchi I, Kawasumi H, Takashima T, Toba H, Kishimoto S
Osaka Prefectural Habikino Hospital, Japan.
Infect Immun. 1994 Dec;62(12):5434-41. doi: 10.1128/iai.62.12.5434-5441.1994.
gamma/delta T cells are likely to participate in the immune response to tuberculous infection in humans. In this study, we carried out an investigation to characterize the responsiveness of gamma/delta T cells from tuberculous patients and healthy individuals to mycobacterial stimulation in vitro. Healthy subjects were assigned to the following two groups: those who had been exposed to tuberculosis (contacts) and those who had not been exposed (noncontacts). The percent gamma/delta T cells in fresh peripheral blood obtained from health care workers who were tuberculin skin test positive and who had constant contact with patients with active tuberculosis (healthy contacts) was significantly higher, whereas healthy noncontacts showed the normal range of gamma/delta T cells. Patients with active pulmonary tuberculosis also had low levels of gamma/delta T cells. HLA-DR antigen-bearing activated gamma/delta T cells were observed in higher percentages among healthy contacts than among healthy noncontacts or patients with pulmonary tuberculosis. In healthy contacts, gamma/delta T cells increased as a percentage of peripheral blood mononuclear cells after in vitro stimulation with purified protein derivative (PPD) tuberculin compared with the percentage of fresh peripheral blood mononuclear cells that they made up, whereas no such increase was observed in patients with tuberculosis or in healthy noncontacts. Phenotypic analysis of the gamma/delta T cells in healthy contacts, which increased in number in vitro in response to PPD, revealed the preferential outgrowth of CD4+ V gamma 2+ gamma/delta T cells. This expansion of gamma/delta T cells by PPD required accessory cells, and it was inhibited by the addition of an antibody against HLA-DR in culture. Proteolytic digestion of PPD showed that gamma/delta T cells increased in number in response to peptide, but not nonpeptide, components of PPD. These findings suggest that gamma/delta T cells, especially CD4+ V gamma 2+ gamma/delta T cells, may participate in the immune surveillance of tuberculous infections in humans.
γ/δ T细胞可能参与人体对结核感染的免疫反应。在本研究中,我们进行了一项调查,以表征结核患者和健康个体的γ/δ T细胞在体外对分枝杆菌刺激的反应性。健康受试者被分为以下两组:曾接触过结核病的人(接触者)和未接触过结核病的人(非接触者)。从结核菌素皮肤试验呈阳性且与活动性肺结核患者有持续接触的医护人员(健康接触者)获得的新鲜外周血中,γ/δ T细胞的百分比显著更高,而健康非接触者的γ/δ T细胞处于正常范围。活动性肺结核患者的γ/δ T细胞水平也较低。在健康接触者中,携带HLA-DR抗原的活化γ/δ T细胞的百分比高于健康非接触者或肺结核患者。在健康接触者中,与新鲜外周血单个核细胞中γ/δ T细胞所占百分比相比,用纯化蛋白衍生物(PPD)结核菌素进行体外刺激后,γ/δ T细胞作为外周血单个核细胞的百分比增加,而在结核病患者或健康非接触者中未观察到这种增加。对在体外因PPD而数量增加的健康接触者中的γ/δ T细胞进行表型分析,发现CD4+ Vγ2+γ/δ T细胞优先增殖。PPD对γ/δ T细胞的这种扩增需要辅助细胞,并且在培养中加入抗HLA-DR抗体可抑制这种扩增。PPD的蛋白水解消化表明,γ/δ T细胞对PPD的肽成分而非非肽成分反应而数量增加。这些发现表明,γ/δ T细胞,尤其是CD4+ Vγ2+γ/δ T细胞,可能参与人体对结核感染的免疫监视。