CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript> Regulatory T Cells Suppress Th17-Responses in an Experimental Colitis Model

Background  

After the recent discovery of Th17 cells, it was proposed that Th17 responses are involved in the pathogenesis of inflammatory bowel diseases (IBD). CD4⁺CD25⁺ regulatory T cells (Treg) are considered to be an attractive tool for the treatment of IBD. Here, we investigated whether Treg are capable of suppressing Th17-mediated colitis.     

Regulatory T cells expanded by rapamycin in vitro suppress colitis in an experimental mouse model

Background

To provide rapid immunosuppression without side effects, we analyzed whether rapamycin alone, and regulatory T cells (Tregs) expanded ex vivo by rapamycin, suppressed colitis in a mouse model.

Methods

Severe combined immunodeficiency (SCID) mice reconstituted with naive CD4⁺ T cells were treated with or without intraperitoneal rapamycin. Body weight was evaluated. CD4⁺ T cells were cultured in the presence of rapamycin for three 7-day rounds of stimulation. The ratio of Tregs to CD4⁺ T cells was analyzed by flow cytometry. Naive CD4⁺ T cells were transferred into SCID mice with CD4⁺ T cells expanded in the presence or absence of rapamycin. Clinical symptoms of colitis, histological changes, and cytokine expression were investigated.

Results

Systemic rapamycin partially prevented the development of colonic inflammation in a transfer model of colitis, but decreased body weight in control mice. With rapamycin, stimulated CD4⁺ T cells expanded eightfold in 3?weeks in vitro, and the proportion of Tregs increased to about 40%. Without rapamycin, CD4⁺ T cells expanded 20-fold in 3?weeks, but the proportion of Tregs remained at about 15%. CD4⁺ T cells expanded with rapamycin prevented the development of colitis in a na?ve CD4⁺ T-cell transfer model, in association with the downregulation of Th1 and Th17 responses.

Conclusions

We demonstrated, for the first time, that CD4⁺ T cells expanded with rapamycin in vitro suppressed colitis. Therefore, rapamycin-expanded Treg transfer therapy is expected to be efficacious for inflammatory bowel disease.     

Comparison between unattended automated office blood pressure and conventional office blood pressure under the environment of health checkup among Japanese general population

Unattended automated office blood pressure (AOBP) measurement has been endorsed as the preferred in‐office measurement modality in recent Canadian and American clinical practice guidelines. However, the difference between AOBP and conventional office blood pressure (CBP) under the environment of a health checkup remains unclear. We aimed to identify the clinical significance of AOBP as compared to CBP under the environment of a health checkup. There were 491 participants (333 females, mean age of 62.5 years) who were at least 20 years old, including 179 participants who were previously diagnosed with hypertension. Mean AOBPs were 131.8 ± 20.9/76.6 ± 11.7 mm Hg, and CBPs were 135.6 ± 21.6/77.3 ± 11.5 mm Hg. There was a difference of 3.9 mm Hg in systolic blood pressure (SBP) and 0.8 mm Hg in diastolic BP between AOBP and CBP. In all participants, SBP and pulse pressure, as well as the white coat effect (WCE), increased with age. The cutoff value used was 140/90 mm Hg for CBP and 135/85 mm Hg for AOBP, and the prevalence of WCE and masked hypertension effect (MHE) was 12.4% and 14.1%, respectively. Even in a health checkup environment of the general population, there was a difference between the AOBP and CBP, and the WCE was observed more strongly in the elderly with a history of hypertension, suggesting that a combination of AOBP with CBP may be useful in detecting WCE and MHE in all clinical scenarios including health checkups, and help solve the “hypertension paradox” not only in Japan but in all over the world.