scholarly journals Disrupted Peyer's patch microanatomy in COVID-19 including germinal centre atrophy independent of local virus

2021 ◽  
Author(s):  
Silvia Cellone Trevelin ◽  
Suzanne Pickering ◽  
Katrina Todd ◽  
Cynthia Bishop ◽  
Michael Pitcher ◽  
...  
Keyword(s):  
T Cell ◽  
Gastrointestinal Symptoms ◽  
Cell Interaction ◽  
Lymphoid Tissues ◽  
Nuclear Density ◽  
Post Mortem ◽  
Gi Tract ◽  
Mass Cytometry ◽  
Germinal Centres ◽  
Disease Impact

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyers patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis.

scholarly journals T Cell/B Cell Interactions in the Establishment of Protective Immunity

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1074
Author(s):  
Julia Ritzau-Jost ◽  
Andreas Hutloff
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Subset ◽  
Cell Interaction ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Lymphoid Tissues ◽  
Pathogen Invasion

Follicular helper T cells (Tfh) are the T cell subset providing help to B cells for the generation of high-affinity antibodies and are therefore of key interest for the development of vaccination strategies against infectious diseases. In this review, we will discuss how the generation of Tfh cells and their interaction with B cells in secondary lymphoid organs can be optimized for therapeutic purposes. We will summarize different T cell subsets including Tfh-like peripheral helper T cells (Tph) capable of providing B cell help. In particular, we will highlight the novel concept of T cell/B cell interaction in non-lymphoid tissues as an important element for the generation of protective antibodies directly at the site of pathogen invasion.

scholarly journals Anti-CD43 Inhibition of  T Cell Homing

1997 ◽  
Vol 185 (8) ◽  
pp. 1493-1498 ◽  
Author(s):  
Leslie M. McEvoy ◽  
Hailing Sun ◽  
John G. Frelinger ◽  
Eugene C. Butcher
Keyword(s):  
Lymph Node ◽  
T Cell ◽  
Inflammatory Responses ◽  
Lymphocyte Activation ◽  
Cell Interaction ◽  
Lymphoid Tissues ◽  
High Endothelial Venules ◽  
Novel Target

The homing of lymphocytes from the blood is controlled by specialized processes of lymphocyte–endothelial cell interaction. Interference with these processes offers the potential to manipulate lymphocyte traffic, and thus to modulate normal and pathologic immune and inflammatory responses. We selected antilymphocyte monoclonal antibodies (mAbs) for inhibition of lymphocyte binding in vitro to lymph node high endothelial venules (HEV), specialized vessels that support lymphocyte recruitment into lymph nodes. mAb L11 blocks T cell binding to lymph node and Peyer's patch HEV and inhibits T cell extravasation from the blood into organized secondary lymphoid tissues. In contrast, L11 has no effect on lymphocyte binding to purified vascular ligands for L-selectin, α4β7, or LFA-1, suggesting that it inhibits by a novel mechanism. The L11 antigen is CD43, a sialomucin implicated in vitro in regulation of lymphocyte activation, whose expression is often dysregulated in the Wiskott-Aldrich syndrome. CD43 represents a novel target for experimental and therapeutic manipulation of lymphocyte traffic and may help regulate T cell distribution in vivo.

scholarly journals T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice.

1995 ◽  
Vol 182 (4) ◽  
pp. 1101-1109 ◽  
Author(s):  
K Nakayama ◽  
K Nakayama ◽  
L B Dustin ◽  
D Y Loh
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Interaction ◽  
Lymphoid Tissues ◽  
Antigenic Peptides ◽  
Spontaneous Apoptosis ◽  
Deficient Mice

Bcl-2 expression is tightly regulated during lymphocyte development. Mature lymphocytes in Bcl-2-deficient mice show accelerated spontaneous apoptosis in vivo and in vitro. Stimulation of Bcl-2-deficient lymphocytes by anti-CD3 antibody inhibited the spontaneous apoptosis not only in T cells but also in B cells. The rescue of B cells was dependent on the presence of T cells, mainly through CD40L and interleukin (IL)-4. Furthermore, we generated Bcl-2-deficient mice transgenic for a T cell receptor or an immunoglobulin, both specific for chicken ovalbumin, to test for antigen-specific T-B cell interaction in the inhibition of the spontaneous apoptosis. The initial T cell activation by antigenic peptides presented by B cells suppressed apoptosis in T cells. Subsequently, T cells expressed CD40L and released ILs, leading to the protection of B cells from spontaneous apoptosis. These results suggest that the antiapoptotic signaling via CD40 or IL-4 may be largely independent of Bcl-2. Engagement of the Ig alone was not sufficient for the inhibition of B cell apoptosis. Thus, the physiological role of Bcl-2 in mature lymphocytes may be to protect cells from spontaneous apoptosis and to extend their lifespans to increase the opportunity for T cells and B cells to interact with each other and specific antigens in secondary lymphoid tissues. Bcl-2, however, appears to be dispensable for survival once mature lymphocytes are activated by antigen-specific T-B cell collaboration.

scholarly journals PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaitao Li ◽  
Zhou Yuan ◽  
Jintian Lyu ◽  
Eunseon Ahn ◽  
Simon J. Davis ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Clinical Success ◽  
Clinical Intervention ◽  
Cell Receptor ◽  
Cell Interaction ◽  
Antigen Recognition ◽  
Inhibitory Function ◽  
Src Homology

AbstractDespite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1’s targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR–pMHC–CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1’s potent inhibitory function and its value as a target for clinical intervention.

scholarly journals The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3050-3059 ◽  
Author(s):  
J Castrop ◽  
D van Wichen ◽  
M Koomans-Bitter ◽  
M van de Wetering ◽  
R de Weger ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Nuclear Dna ◽  
Mouse Cell ◽  
Lymphoid Tissues ◽  
Sequence Motif ◽  
Knock Out ◽  
Putative Transcription Factor ◽  
Knock Out Mice ◽  
T Cell Malignancies

Abstract The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers. TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines. In contrast, expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis. We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein. As expected, the TCF-1 protein was detectable only in cell lines of T lineage. Its expression was always restricted to the nucleus. Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues. Western blotting yielded a set of bands ranging from 25 kD to 55 kD, resulting from extensive alternative splicing. The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation, but was absent from a large number of other hematologic neoplasms. These observations imply a T cell-specific function for TCF-1, a notion corroborated by recent observations on Tcf-1 knock-out mice. In addition, these results indicate that nuclear TCF-1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies.

Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Anthony D. Cristillo ◽  
Mirtha J. Macri ◽  
Barbara E. Bierer
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Signaling Pathways ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Expression Profiles ◽  
Lymphoid Tissues ◽  
Rnase Protection ◽  
Chemokine Expression ◽  
Calcineurin Activity

Abstract The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)–1α, and MIP-1β were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1α and MIP-1β, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity.

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