Andreas Thiel's research while affiliated with Charité Universitätsmedizin Berlin and other places

... Although the demonstration of the direct killing capacities was outside the scope of the study, the secretion of multiple cytokines by vaccine-reactive T cells suggests their killing functional potential as demonstrated in several previous works. 7,[30][31][32][41][42][43][44] TNF-a and IL-2 are secreted by T cells at early stages of immune response, as well as by antigen-reactive Th cells with advanced dif-ferentiation status (central memory Th cells as opposed to highly differentiated effector and Temra subsets). [45][46][47] The role of antigen-reactive Th cells with early differential status is of special interest. ...

... Interestingly, recent results from scRNA-seq have revealed unique complex gene expression signature of CD4 + T cells in aged mice most notably, the aTregs, exhausted, and cytotoxic CD4 + subsets [61]. The CD4 + cytotoxic subset appeared to be dominantly regulated by transcription factors associated with cytotoxicity and T helper 1 (Th1) polarization, including Eomes, Runx2, Runx3, and Tbx21 regulons which are also required for the cytotoxic CD8 lineage [61,62]. This result is in line with our effector-cytokine producing CD4 + T cells data where we observed a significant increase of cytotoxic CD107 + CD4 + T cells and polyfunctional CD107 + IFN-γ + CD4 + T cells lacking typical helper CD40L, IL2 and IL4 expression (Supplemental Fig. 5). ...

... detects antigen-specific CD4 1 T cells according to the expression of CD154 induced during activation (10)(11)(12)(13)(14)(15). In combination with multicolor intracellular cytokine staining, it allows the simultaneous quantitative and qualitative evaluation of CD4 1 T cells specific for a given antigen. ...

... This part is characterized by a higher homology to spike glycoprotein of human endemic "common cold" coronaviruses and contains the S2 subunit of S with the cytoplasmic peptide, the fusion peptide, and the transmembrane domain but not the RBD. S-reactive CD4 + T cells from SARS-CoV-2 patients are further distinct to those from healthy donors as they coexpressed higher levels of CD38 and HLA-DR, indicating their recent in vivo activation (Braun et al. 2020). Potential preexisting cross-reactive T cell immunity to SARS-CoV-2 has broad implications, as it could explain aspects of differential SARS-CoV-2 clinical outcomes, influence epidemiological models of herd immunity, or affect the performance of SARS-CoV-2 candidate vaccines. ...

... The severity of GvHD together with its pharmacological immunosuppressive treatment represents a major limitation of thymus-derived T-cell reconstitution following allo-HSCT [82]. Especially, rabbit antithymocyte globulin preparations given to prevent aGvHD strongly impair thymic-dependent reconstitution [83], at least in part by a direct cytotoxic effect on TECs as shown in in vitro studies (Fig. 3) [84]. Preclinical mouse models of GvHD have shown that the thymus is subjected to several changes in the hematopoietic and stromal compartment as demonstrated by depletion of immature thymocytes and dysplasia of the cortical and medullary stromal compartment with loss of normal thymic architecture [82]. ...

... Plasma cells secreting antibodies specific to that antigen will then be lysed by complement or killed by antibody-dependent cellular cytotoxicity, whereas plasma cells secreting antibodies with a different specificity, including protective memory plasma cells, are spared. The feasibility of this approach has been demonstrated ex vivo and in vivo in a mouse model [76][77][78] . Although the antigen-specific depletion of pathogenic plasma cells offers unprecedented selectivity, its application is limited to autoimmune diseases in which the auto-antigens that drive inflammation are known, for example, myasthenia gravis or anti-NMDA receptor encephalitis. ...

... Recent data have described a lower serological response to an mRNA vaccine in dialysis patients (4) and kidney transplant recipients (5), suggesting an overall diminished vaccine response. Whereas numerous studies have addressed the consequences of conventional vaccines on B and plasma cells (6)(7)(8) and corresponding Ig levels, nothing is known yet about the B lineage consequences in response to an mRNA vaccine among healthy controls and immunocompromised patients. Previous studies in kidney failure patients reported markedly diminished response to vaccinations. ...

... A significant degree of immune cross-reactivity between the spike protein of SARS-CoV-2 and earlier Coronaviruses such as those causing some common colds is known to exist both at the T and B cell levels, in a significant fraction of the population [7-9] -but to explain the exceptionally high efficacy of BNT162b in older adults one would have to postulate their existence in 100 % of older individuals together with an effective boosting effect of the vaccine. While this has not been specifically tested, for example Braun [7] and 66 years [8,9], it is conceivable but does seem a priori unlikely. The same applies to the presence of antibodies in unexposed individuals, tested up to the age of 76 (but only in two donors of this age) by Ng et al. [10]. ...