BACKGROUND. Marked progress is achieved in understanding the physiopathology of coronavirus disease 2019 (COVID-19), which caused a global pandemic. However, the CD4⁺ T cell population critical for antibody response in COVID-19 is poorly understood. METHODS. In this study, we provided a comprehensive analysis of peripheral CD4⁺ T cells from 13 COVID-19 convalescent patients, defined as confirmed free of SARS-CoV-2 for 2 to 4 weeks, using flow cytometry and magnetic chemiluminescence enzyme antibody immunoassay. The data were correlated with clinical characteristics. RESULTS. We observed that, relative to healthy individuals, convalescent patients displayed an altered peripheral CD4⁺ T cell spectrum. Specifically, consistent with other viral infections, cTfh1 cells associated with SARS-CoV-2–targeting antibodies were found in COVID-19 covalescent patients. Individuals with severe disease showed higher frequencies of Tem and Tfh-em cells but lower frequencies of Tcm, Tfh-cm, Tfr, and Tnaive cells, compared with healthy individuals and patients with mild and moderate disease. Interestingly, a higher frequency of cTfh-em cells correlated with a lower blood oxygen level, recorded at the time of admission, in convalescent patients. These observations might constitute residual effects by which COVID-19 can impact the homeostasis of CD4⁺ T cells in the long-term and explain the highest ratio of class-switched virus-specific antibody producing individuals found in our severe COVID-19 cohort. CONCLUSION. Our study demonstrated a close connection between CD4⁺ T cells and antibody production in COVID-19 convalescent patients. FUNDING. Six Talent Peaks Project in Jiangsu Province and the National Natural Science Foundation of China (NSFC).

For many decades, T helper 2 (T_H2) cells have been considered to predominantly regulate the pathogenic manifestations of allergic asthma, such as IgE-mediated sensitization, airway hyperresponsiveness, and eosinophil infiltration. However, recent discoveries have significantly shifted our understanding of asthma from a simple T_H2 cell-dependent disease to a heterogeneous disease regulated by multiple T cell subsets, including T follicular helper (T_FH) cells. T_FH cells, which are a specialized cell population that provides help to B cells, have attracted intensive attention in the past decade because of their crucial role in regulating antibody response in a broad range of diseases. In particular, T_FH cells are essential for IgE antibody class-switching. In this review, we summarize the recent progress regarding the role of T_FH cells and their signature cytokine interleukin (IL)-21 in asthma from mouse studies and clinical reports. We further discuss future therapeutic strategies to treat asthma by targeting T_FH cells and IL-21.

Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8⁺T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8⁺T cell-mediated immunopathology.

Initially identified as a T cell and mast cell growth factor, interleukin (IL)‑9 has long been recognized as an important mediator of asthma. Recently, accumulating results from transgenic mice demonstrated that systemic or lung‑specific overexpression of IL‑9 caused asthma‑associated symptoms. Moreover, anti‑mIL‑9 antibody (Ab) blocking treatment alleviated disease in animal models of asthma. In light of the large quantity of data from the murine models, MEDI‑528, a humanized anti‑IL‑9 monoclonal Ab has been produced to assess the activity of IL‑9 on human asthma. In order to ascertain whether it is a successful translation from bench to bedside, the biological features of IL‑9 were evaluated and up‑to‑date information regarding the role of IL‑9 in different experimental murine models and human asthma were summarized.

The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared with other vaccine platforms. Here, we recruited 88 healthy individuals who received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4 ⁺ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the second and third doses of vaccine induced robust spike-specific neutralizing antibodies, with a third vaccine further increasing the overall magnitude of antibody response and neutralization against Omicron sublineages B.1.1.529, BA.2, BA.4/BA.5, and BA.2.75.2. Spike-specific CD4 ⁺ T cells and circulating T follicular helper (cTfh) cells were markedly increased by the second and third dose of CoronaVac vaccine, accompanied by altered composition of functional cTfh cell subsets with distinct effector and memory potential. Additionally, cTfh cells were positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine–induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.