333,573 research outputs found
Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses
No full textThe host responds to lymphopenic environments by acute homeostatic proliferation of T lymphocytes, which acquire phenotypes similar to memory cells. Using T-cell knockout (KO) mice adoptively reconstituted with splenocytes from immunologically naive mice, we examined the immune responses of an immune system derived from homeostatically proliferating (HP) T cells. HP cells mounted relatively normal acute CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV), but with altered T-cell receptor (TCR) repertoires, and they became functional memory cells capable of recall responses. Although homeostatic proliferation does not normally fully restore T-cell numbers, the CD8(+) T-cell pool was completely restored in T-cell KO mice after LCMV infection. CD4 T-cell responses were lower and not fully restored but seemed sufficient to allow for complete differentiation of CD8 memory T cells. The LCMV-immune HP mouse had an immune repertoire heavily biased with LCMV epitope-specific T cells with oligoclonal expansions. LCMV-immune HP mice had reduced cross-reactive and non-cross-reactive CD8 T-cell responses when challenged with a T cell-cross-reactive virus. Thus, whereas an HP immune system is capable of mounting relatively normal acute and memory CD8 T-cell responses, the narrowing of the T-cell repertoire may reduce immune responses to subsequently encountered pathogens.Immunology and Virolog
Celebration of the Life of Edward K. T. Chen
No full textEdward C. M. Chen is the son of Edward K. T. Chen
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Cd1d-Independent Developmental Acquisition of Prompt Il-4 Gene Inducibility in Thymus Cd161(Nk1)–Cd44lowcd4+Cd8– T Cells Is Associated with Complementarity Determining Region 3-Diverse and Biased V 2/V 7/V 8/V 3.2 T Cell Receptor Usage
No full textAmong Ag-inexperienced naive T cells, the CD1d-restricted NKT cell that uses invariant TCR- -chain is the most widely studied cell capable of prompt IL-4 inducibility. We show in this study that thymus CD161–CD44 lowCD4+CD8– T cells promptly produce IL-4 upon TCR stimulation, a response that displays biased V (2/7/8) and V 3.2 TCR usage. The association of V family bias and IL-4 inducibility in thymus CD161–CD44 lowCD4+CD8– T cells is found for B6, B10, BALB/c, CBA, B10.A(4R), and ICR mouse strains. Despite reduced IL-4 inducibility, there is a similarly biased V (2/ 7/8) TCR usage by IL-4 inducibility+ spleen CD161–CD44 lowCD 4+CD8– T cells. Removal of -galacotosylceramide/CD1d - binding cells from CD161–CD44lowCD4+CD8– thymocytes does not significantly affect their IL-4 inducibility. The development of thymus CD161–CD44lowCD4+CD8– T cells endowed with IL-4 inducibility and their associated use of V (2/7 /8) are 2-microglobulin-, CD1d-, and p59fyn- independent. Thymus CD161– CD44lowCD4+CD8– T cells produce low and no IFN- inducibility in response to TCR stimulation and to IL-12 + IL-18, respectively, and they express diverse complementarity determining region 3 sequences for both TCR- - and - -chains. Taken together, these results demonstrate the existence of a NKT cell distinct, TCR- repertoire diverse naive CD4+ T cell subset capable of prompt IL-4 inducibility. This subset has the potential to participate in immune response to a relatively large number of Ags. The more prevalent nature of this unique T cell subset in the thymus than the periphery implies roles it might play in intrathymic T cell development and may provide a framework upon which mechanisms of developmentally regulated IL-4 gene inducibility can be studied
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis
No full textChunhui Jiang,1– 3 Jiani Chen,1– 3 Tong Sun,2,3 Jiaqin Xu,2,3 Hongguo Zhu,2,3 Jiaxi Chen1– 3 1School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Department of Laboratory Medicine, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, People’s Republic of ChinaCorrespondence: Jiaxi Chen, Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen Street, Linhai, Zhejiang Province, 317000, People’s Republic of China, Tel +86-13606652901, Email [email protected]: The pathogenesis of T cell subsets in sepsis during the body’s resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis.Patients and Methods: Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC.Results: Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6− Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6− Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis.Conclusion: We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells’ function and regulatory mechanisms during sepsis pathogenesis.Keywords: scRNA-seq, pySCENIC, GRN, reference mappin
H ? filtering for stochastic singular fuzzy systems with time-varying delay
Full text linkThis paper considers the H? filtering problem
for stochastic singular fuzzy systems with timevarying
delay. We assume that the state and measurement
are corrupted by stochastic uncertain exogenous
disturbance and that the system dynamic is modeled
by Ito-type stochastic differential equations. Based on
an auxiliary vector and an integral inequality, a set of
delay-dependent sufficient conditions is established,
which ensures that the filtering error system is e?t -
weighted integral input-to-state stable in mean (iISSiM).
A fuzzy filter is designed such that the filtering
error system is impulse-free, e?t -weighted iISSiM and
the H? attenuation level from disturbance to estimation
error is belowa prescribed scalar.Aset of sufficient
conditions for the solvability of the H? filtering problem
is obtained in terms of a new type of Lyapunov
function and a set of linear matrix inequalities. Simulation
examples are provided to illustrate the effectiveness
of the proposed filtering approach developed in
this paper
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