[The effect of CD4+ CD25+ regulatory T cell inactivation combined with levofloxacin on murine tuberculosis].
OBJECTIVE
To investigate the effects of inactivation of CD(4)(+)CD(25)(+) regulatory T cells (Treg) combined with the administration of levofloxacin (LFX) on the cellular immune response of murine tuberculosis.


METHODS
Inactivation of Treg was achieved by intraperitoneal injection of anti-CD(25), clone PC61. Female C57BL/6 mice were divided into 4 groups, PC61 alone, LFX alone, PC61 plus LFX, and the control, with 19 mice in each group. The LFX group and the control group were treated with rat-IgG isotope control. Mice were inoculated with H(37) Rv (1 x 10(6) CFU) via the tail vein 3 days later. From the 2nd day, the LFX group and the PC61 plus LFX group received intragastric administration of LFX at 200 mg x kg(-1) x d(-1) per mouse for 45 days. Blood and spleen Tregs were measured by flow cytometry. The cellular immune response and pulmonary histopathology at different time points were also evaluated after infection.


RESULTS
At the 10th and 30th day, the ratio of CD(4)(+)CD(25)(+)/CD(4)(+)T cells in the spleen was (30 +/- 4)% and (17.3 +/- 1.6)% respectively in the control group, (21 +/- 4)% and (16.1 +/- 1.3)% respectively in the PC61 group, (44 +/- 6)% and (24.7 +/- 2.0)% respectively in the LFX group, (24 +/- 3)% and (10.4 +/- 1.0)% respectively in the PC61 plus LFX group. The differences were significant between groups (q = 3.62 - 5.56, P < 0.05), but the difference between the PC61 plus LFX group and the PC61 group at the 10th day. Same results were obtained from the peripheral blood. PC61 plus LFX therapy resulted in BCG specific cytokine response (IL-17, IFN-gamma, TNF-alpha) from murine spleen cells at the 10th and the 30th day, and also in milder pathologic changes and the lowest mortality.


CONCLUSIONS
The cellular immune response was enhanced by Treg inactivation and LFX therapy, which decreased the pathologic changes and the mortality of murine tuberculosis.
Tong
Xin-Deng
XD
Renmin Hospital of Wuhan University, Wuhan 430060, China.
Li
Mei-Zhong
MZ
Zhou
Bo-Ping
BP
Chen
Xin-Chun
XC
Peng
Yan-Zhong
YZ
Yue
Xiao-Hua
XH
Gou
Ji-Zhou
JZ
Tang
Zhi-Jiao
ZJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005260:Female; D064704:Levofloxacin; D051379:Mice; D008810:Mice, Inbred C57BL; D015242:Ofloxacin / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin