T Cells of Atopic Asthmatics Preferentially Infiltrate Into Human Bronchial Xenografts in SCID Mice

Abstract

T cells play an important role in the pathogenesis of bronchial asthma. However, it is not completely known how circulating lymphocytes infiltrate into the airways of asthmatic patients. Because SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in SCID mice. We transplanted human bronchi into the subcutaneum of SCID mice and i.p. injected PBMCs that were obtained from patients with atopic asthma, atopic dermatitis and rheumatoid arthritis, and normal subjects (asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice). There was no difference in the percentage of CD3-, CD4-, CD8-, CD25-, CD45RO-, CD103-, and cutaneous lymphocyte Ag-positive cells in PBMCs among the patients with asthma, dermatitis, rheumatoid arthritis, and normal subjects, and CD3-positive cells in peripheral blood of asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice. The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice. IL-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than those in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL-2 mRNA or IFN-γ mRNA between them. These findings suggest that T cells, especially Th2-type T cells, of asthmatics preferentially infiltrate into the human bronchi.

Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity

“…In particular, lymphocytes obtained from peripheral blood in asthmatics demonstrate a predominance of T-helper lymphocyte type 2 (T H 2, IL 4 producing) immune responses relative to T H 1 (IFN-␥ producing) (33,124). Moreover, Tsumori and colleagues (147) showed that T cells from asthmatic subjects, in particular T H 2 cells, preferentially migrate to bronchial tissue (see Fig. 3), and de Blic and colleagues (28) found that bronchoalveolar lavage samples obtained from highly symptomatic children with asthma show substantially increased ratios of the protein products IL-4/IFN-␥.…”

“…We propose that exercise might contribute to this imbalance, leading to exercise-induced bronchoconstriction (EIB). [Data redrawn from Tsumori et al (147).] Table 1.…”

Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

“…Because it has been shown that several cytokines, such as IL-4, IL-5, IL-2, IFN-γ, were detectable in SCID mice transplanted with human PBLs [41], we only included IL-2 as the representative cytokine in the current study. We found that the isolated PBLs from the serum of model mice did produce certain cytokines, i.e., IL-2 ( Fig.…”

Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma

“…In immune responses, homing of lymphocytes from blood into organs is mediated by a sequential interaction between the lymphocytes and the vascular endothelium in specialized post‐capillary venules (5). In inflamed skin, T cells express the cutaneous lymphocyte associated antigen (CLA) and P‐selectin ligand and the vascular epithelium expresses E‐selectin and P‐selectin (6); however, the adhesion molecules and chemokines for T‐cell homing into airways, lungs and bronchi are not well‐clarified (7).…”

“…. In inflamed skin, T cells express the cutaneous lymphocyte associated antigen (CLA) and Pselectin ligand and the vascular epithelium expresses E-selectin and P-selectin (6); however, the adhesion molecules and chemokines for T-cell homing into airways, lungs and bronchi are not well-clarified (7).…”