Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4 + and CD8 + T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4 + and CD8 + T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4 + and CD8 + T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals > 65 years old. Scarcity of naive T cells was also associated with ageing and poor disease outcomes. A parsimonious explanation is that coordinated CD4 + T cell, CD8 + T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between ageing and impaired adaptive immune responses to SARS-CoV-2.

T follicular helper (T FH ) cells are a distinct type of CD4 + T cells that are essential for most antibody and B lymphocyte responses. T FH cell regulation and dysregulation is involved in a range of diseases. Bcl-6 is the lineage defining transcription factor of T FH cells and its activity is essential for T FH cell differentiation and function. However, how Bcl-6 controls T FH biology has largely remained unclear, at least in part due to intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl-6 exhibited negative autoregulation and controlled pleiotropic attributes of T FH differentiation and function, including migration, costimulation, inhibitory receptors, and cytokines, via multiple repressor-of-repressor gene circuits.

TSA attenuated the development of allergic airway inflammation by decreasing expression of the Th2 cytokines, IL-4 and IL-5, and IgE, which resulted from reduced T cell infiltration. Our results suggest that HDAC inhibition may attenuate the development of asthma by a T cell suppressive effect.

HighlightsB cell help, afforded by T cells, is an essential process of adaptive immunity.The transcription factor B cell lymphoma 6 (Bcl6), by serving as an apex of a repressor-of-repressors network, can provide further insights into follicular helper T cell (T FH ) regulation in mice and humans.Bcl6 is essential for T FH differentiation and harbors various significant activities, including inhibition of Prdm1 expression.We posit that Bcl6 can control non-T FH and T FH genes by at least two modes of action: direct repression and repressionof-repressor mechanisms.