CD4 + regulatory T cells (T reg ) expressing the forkhead box protein 3 (FOXP3)transcription factor (T regs ) are instrumental for the prevention of autoimmune diseases. There is increasing evidence that the human T regulatory population is highly heterogeneous in phenotype and function. Numerous studies conducted in human autoimmune diseases have shown that T reg cells are impaired either in their suppressive function, in number, or both. However, the contribution of the FOXP3 + T reg subpopulations to the development of autoimmunity has not been delineated in detail. Rare genetic disorders that involve deficits in T reg function can be studied to develop a global idea of the impact of partial or complete deficiency in a specific molecular mechanism involved in T reg function. In patients with reduced T reg numbers (but no functional deficiency), the expansion of autologous T reg cells could be a suitable therapeutic approach: either infusion of invitro autologous expanded cells, infusion of interleukin (IL)-2/anti-IL-2 complex, or both. T reg biology-based therapies may not be suitable in patients with deficits of T reg function, unless their deficit can be corrected in vivo/in vitro.Finally, it is critical to consider the appropriate stage of autoimmune diseases at which administration of T reg cellular therapy can be most effective. We discuss conflicting data regarding whether T reg cells are more effectual at preventing the initiation of autoimmunity, ameliorating disease progression or curing autoimmunity itself.

It is currently unknown whether acquired immunity to common alpha- and beta-coronaviruses provides cross-protection against SARS-CoV-2. In this study, we found that certain patient sera and intravenous immunoglobulins (IVIG) collected prior to the COVID-19 outbreak were cross-reactive to SARS-CoV-2 full-length Spike, S2 domain, and nucleoprotein. However, their presence did not translate into neutralizing activity against SARS-CoV-2 in vitro. Importantly, we detected serum IgG reactivity to common coronaviruses in the early sera of patients with severe COVID-19 before the appearance of anti-SARS-CoV-2 antibodies. Collectively, the results of our study indicate that pre-existing immunity to common coronaviruses does not confer cross-protection against SARS-CoV-2 in vivo.