Anti-CD3 Antibody Decreases Inflammation and Improves Outcome in a Murine Model of Pneumocystis Pneumonia

被引:16
作者
Bhagwat, Samir P.
Wright, Terry W. [2 ]
Gigliotti, Francis [1 ,2 ]
机构
[1] Univ Rochester, Med Ctr, Dept Pediat, Sch Med & Dent, Rochester, NY 14642 USA
[2] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA
基金
美国国家卫生研究院;
关键词
CARINII-PNEUMONIA; T-CELL; PULMONARY INFLAMMATION; MONOCLONAL-ANTIBODY; MICE; EXPRESSION; MECHANICS; DAMAGE; AIDS; CD4+;
D O I
10.4049/jimmunol.0901864
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
The T cell-mediated immune response elicited by Pneumocystis plays a key role in pulmonary damage and dysfunction during Pneumocystis carinii pneumonia (PcP). Mice depleted of CD4(+) and CD8(+) T cells prior to infection are markedly protected from PcP-related respiratory deficit and death, despite progressive lung infection. However, the therapeutic effectiveness of Ab-mediated disruption of T cell function in mice already displaying clinical symptoms of disease has not been determined. Therefore, a murine model of PcP-related immune reconstitution inflammatory syndrome was used to assess whether Ab to the pan-T cell molecule CD3 is effective for reducing the severity of PcP when administered after the onset of disease. Mice that received antiCD3 Ab exhibited a rapid and dramatic halt in the PcP-associated pulmonary function decline within I week after treatment, and a striking enhancement of survival rate compared with mice receiving the control Ab. Physiologic improvement in anti-CD3 treated mice was associated with a significant reduction in the number of CD4(+) and CD8(+) T cells recovered in lung lavage fluid. This effectiveness of anti-CD3 was noted whether the mice also received antibiotic therapy with trimethoprim-sulfamethoxazole. These data suggest that monoclonal Ab-mediated disruption of T cell function may represent a specific and effective adjunctive therapy to rapidly reverse the ongoing pathologic immune response occurring during active PcP. Thus, the anti-human CD3 monoclonal Ab OKT3, which is already in clinical use, has the potential to be developed as an adjunctive therapy for PcP. The Journal of Immunology, 2010, 184: 497-502.
引用
收藏
页码:497 / 502
页数:6
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