Kinetics of adaptive immunity to Haemophilus influenzae type b meningitis in transgenic mice: evidence from diverse expression of double T1/T2 transgenes and Th1/Th2-related cytokines.
To investigate the kinetic changes in adaptive immunity during experimental Haemophilus influenzae type b (Hib) meningitis, we established a murine meningitis model based on T1/T2 doubly transgenic mice. These mice carry two transgenes that express two distinct cell-surface markers: a human Thy1 transgene (hThy1) under the control of the murine IFN-gamma promoter, and a murine Thy1.1 transgene (mThy1.1) under the control of the murine IL-4 promoter, designated T1 and T2, respectively. Mice infected with Hib displayed severest symptoms and lowest total splenocyte counts on day 3 after infection. Simultaneously, we examined the significantly low percentage of CD19+ B cells, the relatively high level of CD4+ T cells and significantly high percentage of CD8+ T cells in Hib-infected mice. Furthermore, we observed the early induction of both Th1 and Th2 responses, in terms of the augmentation of Th1 cells (IFN-gamma-producing CD4+ T cells) and Th2 cells (IL-4-producing CD4+ T cells) in Hib-infected mice. On day 7 after infection, the Th1 response gradually declined and the Th2 response rather sustained. Two weeks after infection, both Th1 and Th2 cells were barely detectable. Moreover, we demonstrated using an antigen-specific re-stimulation test to analyze the effector function of lymphocyte subsets that CD8+ T cells contributed to more predominantly production of IFN-gamma than CD4+ T cells did; and CD4+ T cells partly contributed to the secretion of IL-4 from flowcytometry of intracellular cytokine staining. Our results support that these transgenic mice provide an available model to dissect the complex kinetic change of adaptive immunity in bacterial infectious diseases.
Chen
Shyi-Jou
SJ
The Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Liao
Ching-Len
CL
Hsieh
Shie-Liang
SL
Chu
Mong-Ling
ML
Fang
Mei-Cho
MC
Sytwu
Huey-Kang
HK
Wang
Chih-Chien
CC
D000222:Adaptation, Physiological; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D008583:Meningitis, Haemophilus / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D018800:Thy-1 Antigens / Q000235:genetics
D000942:Antigens, Bacterial; D016207:Cytokines; D018800:Thy-1 Antigens; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA