Early Changes in Circulatory T Helper Type 1, 2, and 17 Cells of Patients with Out-of-Hospital Cardiac Arrest after Successful Cardiopulmonary Resuscitation

Background： Immune disorder is an important feature of patients with out-of-hospital cardiac arrest （OHCA） after the return of spontaneous circulation （ROSC）. We investigated the expression of circulatory T helper type （Th）1, Th2, and Th 17 cells to explore the early immune alteration in OHCA patients after ROSC. Methods： During July-September 2016 and March-September 2017, 65 consecutive OHCA patients with ROSC 〉 12 h and 30 healthy individuals were enrolled in this study. Clinical and 28-day survival data were collected. Peripheral blood samples were analyzed to evaluate the expression of Th1/Th2/Th 17 cells by flow cytometry from OHCA patients after ROSC on days l and 3 and from healthy individuals. Results： Compared with healthy individuals, T lymphocyte counts and Thl cell counts decreased on days 1 and 3 after ROSC （1464 [1198, 2152] vs. 779 [481, 1140] vs. 581 [324, 1118/μl,χ^2= 30.342, P 〈 0.001; 154 [90, 246] vs. 39 [19, 78] vs. 24 [12, 53]μl, χ^2 = 42.880, P〈 0.001）, and Th2 and Th17 cell counts decreased on day 3 （17.0 [10.8, 24.0] vs. 9.0 [3.0, 15.5]μl, Z= -3.228, P= 0.001; 4.7 [2.7, 9.1] vs. 2.7 [1.0, 6.5]μl, Z = -2.294, P = 0.022）. No change in CD4＋/CD3＋ lymphocyte ratio was seen on day 1 or day 3 （57.9 [49.4, 63.0] vs. 55.4 [46.5, 66.5] vs. 55.4 [50.2, 67.0]%, χ^2 = 0.171, P = 0.918）. Th1/CD4＋ lymphocyte ratio decreased on days 1 and 3 （19.0 [14.0, 24.9] vs. 9.3 [4.6, 13.9] vs. 9.5 [4.9, 13.6]%, χ^2= 25.754, P 〈 0.001）, and Th2/CD4＋ lymphocyte ratio increased on day 1 and decreased on day 3 （1.9 [1.2, 2.5] vs. 2.5 [1.6, 4.0] vs. 1.9 [1.6, 3.81%,χ^2= 6.913, P = 0.032）. Thl/Th2 cell ratio also decreased on both clays （9.4 [7.3, 13.5] vs. 3.1 [1.9, 5.6] vs. 4.2 [2.8, 5.9], χ^2 = 44.262, P 〈 0.001 ）. Despite an upward trend in the median of Th 17/CD4＋ lymphocyte ratio in OHCA patients, there was no significant difference compared with healthy individuals （0.9 [0.4, 1.2] vs. 0.7 [0.4, 1.2] vs. 0.6 [0.3, 1.01%, χ^2= 2.620, P = 0.270）. The dynamic expression of Th1/Th2/Th 17 cells on days 1 and 3 were simultaneously analyzed in 28/53 OHCA patients who survived 〉3 days; patients were divided into survivors （n = 10） and nonsurvivors （n = 18） based on 28-day survival. No significant differences in Th1/Th2/Th 17 cell counts, ratios in CD4＋ lymphocytes, and Th1/Th2 cell ratio were seen between survivors and nonsurvivors on both days （all P 〉 0.05）. There was no difference over time in both survivors and nonsurvivors （all P 〉 0.05）. Conclusion： Downregulated T lymphocyte counts, including Th1/Th2/Th17 subsets and Th1/Th2 cell ratio imbalance, occur in the early period after ROSC, that may be involved in immune dysfunction in OHCA patients.

Increased Expression of PI-3K in Asthmatic Rat T Lymphocytes

In order to explore the expression of PI-3K in T lymphocytes of asthmatic rats and the relationship between PI-3K and activation of T lymphocytes, 24 Wistar rats were randomly divided into 4 groups： normal control group, asthmatic one-week group, asthmatic two-week group and asthmatic four-week group. T cells were purified from blood of each rat and the expression of PI-3K was observed by immunocytochemical fluorescence staining, the serniquantitative fluorescence intensity was measured by HPIAS-2000 analytic software, and the expression of IL-4 in supernatants was detected by ELISA. The results showed that the fluorescence intensity of T lymphocytes in asthmatic groups was significantly higher than that in normal control （P〈0.001）, indicating that the expression of PI-3K in T lymphocytes of asthmatic rats was significantly higher than that in those of normal controls, and the difference between acute and chronic stage asthmatic groups was significant （P〈0.05）. The expression levels of IL-4 protein in supernatants of asthmatic T lymphocytes were significantly higher than those in the normal controls （P〈0.05）. There was a significant positive correlation between the expression of PI-3K in T lymphocytes and the IL-4 protein expression in supernatants （r=0.583, P〈0.01）. It was suggested that PI-3K signal pathway may participate in the processes of activation and other cytological effects of asthmatic T lymphocytes, thus may play an important roles in the pathogenesis of asthma.

Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses

The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.

Current understanding of Th2 cell differentiation and function

Helper T cell(Th)has been identified as a critical immune cell for regulating immune response since 1980s.The type 2 helper Tcell(Th2),characterized by the production of interleukin-4(IL-4),IL-5 and IL-13,plays a critical role in immune response against helminths invading cutaneous or mucosal sites.It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea.Currently,most studies have shed light on Th2 cell function and behavior in specific diseases,such as asthma and helminthes inflammation,but not on Th2 cell itself and its differentiation.Based on different cytokines and specific behavior in recent research,Th2 cell is also regarded as new subtypes of T cell,such as IL-9 secreting T cell(Th9)and CXCR5+T follicular helper cells.Here,we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.

Pathologically expanded peripheral CD4^(+)PD-1^(+)Foxp3^(−) T-cell subset promotes B-cell hyperactivity in patients with rheumatoid arthritis

Background:Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive polyarthritis, and abnormal T-B-cell interactions may contribute to its pathogenesis. This study aimed to investigate the characteristics and roles of CD4^(+) programmed death 1 (PD-1)^(+)Foxp3^(−) T cells in relation to the B-cell response in patients with RA. Methods:This study included 155 patients with RA and 36 age- and sex-matched healthy controls (HCs) from the Second Hospital of Dalian Medical University in China. Flow cytometry was used to assess the proportion and properties of peripheral CD4^PD-1^(−)Foxp3^(+) T cells, including their proliferation, activation, cytokine production, and capacity to induce B-cell differentiation. Results:The proportion of CD4^(+)PD-1^(+)Foxp3^(−)T cells was increased in patients with RA compared with HCs ([10.78 ± 0.60]% vs. [5.67 ± 0.40]%, p < 0.001), and this was positively associated with the B-cell response. Compared with CD4^PD-1 ^(+)Foxp3 ^(+) T cells, CD4^(+)PD-1^(+)Foxp3^(−)T cells from patients with RA exhibited increased expression of Ki67 ([6.52 ± 0.41]% vs. [3.87 ± 0.42]%, p < 0.01) and activation markers, produced higher levels of cytokines, and showed enhanced B-cell differentiation. Furthermore, anti-interleukin-6R antagonists decreased the proportion, activation, and cytokine production of CD4^(+)PD-1^(+)Foxp3^(−)T cells in vitro. The frequency of type 2 CD4^(+)PD-1^(+)Foxp3^(−)T cells was significantly higher in patients with RA than that in HCs ([37.27 ± 1.43]% vs. [29.05 ± 1.30]%, p < 0.05). Conclusions:Peripherally expanded CD4^(+)PD-1^(+)Foxp3^(−)T cells in patients with RA, which induced B-cell hyperactivity, may be inclined toward type 2 helper T cells. Our findings revealed a novel T-cell subset that contributes to B-cell hyperactivity in the pathogenesis of RA.