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T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Preexisting T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of “common cold”. In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from a- and b-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between a- and b-hCoVs. In some, nonSARS hCoV-specific T cells demonstrated a prominent non-reciprocal crossreactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited crossrecognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs. [ABSTRACT FROM AUTHOR]

The article investigates the DR3/DQ2-restricted T cell response to wild-type human Laminin (hLa) and a truncated form of mutant La. The researchers identified multiple DR3-restricted epitopes of hLa. The results indicate that truncation of La produced by somatic mutation or possibly granzyme B-mediated cleavage alters the immunodominance hierarchy of T cell responsiveness to hLa and may be a factor in the initiation or maintenance of anti-La autoimmunity.

Background: Acute Kraft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplintation (ailo-HSCT). We examined the association between the composition of the cell subsets present in allogeneic grafts (allografts) and the occurrence and severity of aGVHD in pediatric patients. Met/zods.· We retrospectively analyzed 80 consecutive pediatric patients undergoing allo-HSCT at our center. Results.· Both univariate and multivariate analyses showed that the number of CD34 and CD3- T-cells iii 8110- grafts were the two highest risk factors associated with Ii-IV aGVHD. Using receiver operating characteristic analysis, the cutoff levels of the allo-HSCT cell doses were used to divide the recipients into low-dose and highdose groups. The 100-day cumulative incidence of II-IV aGVHD in the high-dose CD34 - and CD3 T-cells group was significantly higher than that of the low-dose group (CD34 : 57% vs. 29%, p = 0.009; CDS-: 63% vs. 180/0, p < 0.001). No other clinical factors or cell subsets correlated with aGVHD incidence. Conclusions: Our analysis indicates that the CD:34'" and CD3 ' T-cell numbers in the allografts could be the risk factors for the development of severe aGVHD (level II-IV). Further studies should aim to optimize the critical number of CD34- and CD3- T-cells to reduce the risk of severe aGVHD occurrence in pediatric patients. [ABSTRACT FROM AUTHOR]

A human La/Sjogren's syndrome-B (hLa(-specific TCR/hLa neo-self-Ag double-transgenic (Tg) mouse model was developed and used to investigate cellular tolerance and autoimmunity to the ubiquitous RNA-binding La Ag often targeted in systemic lupus erythematosus and Sjogren's syndrome. Extensive thymic clonal deletion of CD4+ T cells occurred in H-2k/k double-Tg mice presenting high levels of the I-Ek-restricted hLa T cell epitope. In contrast, deletion was less extensive in H-2k/b double-Tg mice presenting lower levels of the epitope, and some surviving thymocytes were positively selected as thymic regulatory T cells (tTreg). These mice remained serologically tolerant to hLa and healthy. 11-2k/b double-Tg mice deficient of all endogenous Tcra genes, a deficiency known to impair Treg development and function, produced IgG anti-hLa autoantibodies and displayed defective tTreg development. These autoimmune mice had interstitial lung disease characterized by lymphocytic aggregates containing Tg T cells with an activated, effector memory phenotype. Salivary gland infiltrates were notably absent. Thus, expression of nuclear hLa Ag induces thymic clonal deletion and tTreg selection, and lymphocytic infiltration of the lung is a consequence of La-specific CD4+ T cell autoimmunity. [ABSTRACT FROM AUTHOR]