From adb80cb94ec0ae23c4ee1d8006cbd16c17c6fc55 Mon Sep 17 00:00:00 2001 From: ndwarshuis Date: Sun, 1 Aug 2021 13:17:53 -0400 Subject: [PATCH] ADD beefier background section on integrin pathways --- tex/references.bib | 90 ++++++++++++++++++++++++++++++++++++++++++++++ tex/thesis.tex | 46 +++++++++++++++++++++--- 2 files changed, 132 insertions(+), 4 deletions(-) diff --git a/tex/references.bib b/tex/references.bib index 63371d7..73b8479 100644 --- a/tex/references.bib +++ b/tex/references.bib @@ -1400,6 +1400,96 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec publisher = {Springer Science and Business Media {LLC}}, } +@Article{Dustin2001, + author = {Michael L Dustin and Antonin R de Fougerolles}, + journal = {Current Opinion in Immunology}, + title = {Reprograming T cells: the role of extracellular matrix in coordination of T cell activation and migration}, + year = {2001}, + month = {jun}, + number = {3}, + pages = {286--290}, + volume = {13}, + doi = {10.1016/s0952-7915(00)00217-x}, + publisher = {Elsevier {BV}}, +} + +@Article{Ebnet1996, + author = {Klaus Ebnet and Eric P. Kaldjian and Arthur O. Anderson and Stephen Shaw}, + journal = {Annual Review of Immunology}, + title = {{ORCHESTRATED} {INFORMATION} {TRANSFER} {UNDERLYING} {LEUKOCYTE} {ENDOTHELIAL} {INTERACTIONS}}, + year = {1996}, + month = {apr}, + number = {1}, + pages = {155--177}, + volume = {14}, + doi = {10.1146/annurev.immunol.14.1.155}, + publisher = {Annual Reviews}, +} + +@Article{Gunzer2000, + author = {Matthias Gunzer and Angelika Schäfer and Stefan Borgmann and Stephan Grabbe and Kurt S. Zänker and Eva-Bettina Bröcker and Eckhart Kämpgen and Peter Friedl}, + journal = {Immunity}, + title = {Antigen Presentation in Extracellular Matrix}, + year = {2000}, + month = {sep}, + number = {3}, + pages = {323--332}, + volume = {13}, + doi = {10.1016/s1074-7613(00)00032-7}, + publisher = {Elsevier {BV}}, +} + +@Article{Aoudjit2000, + author = {Aoudjit, F. and Vuori, K.}, + journal = {Blood}, + title = {Engagement of the alpha2beta1 integrin inhibits Fas ligand expression and activation-induced cell death in T cells in a focal adhesion kinase-dependent manner.}, + year = {2000}, + issn = {0006-4971}, + month = mar, + pages = {2044--2051}, + volume = {95}, + abstract = {T-cell receptor (TCR)-mediated apoptosis, also known as activation-induced cell death (AICD), plays an important role in the control of immune response and in the development of T-cell repertoire. Mechanistically, AICD has been largely attributed to the interaction of Fas ligand (Fas-L) with its cell surface receptor Fas in activated T cells. Signal transduction mediated by the integrin family of cell adhesion receptors has been previously shown to modulate apoptosis in a number of different cell types; in T cells, integrin signaling is known to be important in cellular response to antigenic challenge by providing a co-stimulatory signal for TCR. In this study we demonstrate that signaling via the collagen receptor alpha2beta1 integrin specifically inhibits AICD by inhibiting Fas-L expression in activated Jurkat T cells. Engagement of the alpha2beta1 integrin with monoclonal antibodies or with type I collagen, a cognate ligand for alpha2beta1, reduced anti-CD3 and PMA/ionomycin-induced cell death by 30% and 40%, respectively, and the expression of Fas-L mRNA by 50%. Further studies indicated that the alpha2beta1-mediated inhibition of AICD and Fas-L expression required the focal adhesion kinase FAK, a known component in the integrin signaling pathways. These results suggest a role for the alpha2beta1 integrin in the control of homeostasis of immune response and T-cell development. (Blood. 2000;95:2044-2051)}, + chemicals = {CD3 Complex, Cell Adhesion Molecules, FASLG protein, human, Fas Ligand Protein, Integrins, Ionophores, Membrane Glycoproteins, Protein Synthesis Inhibitors, RNA, Messenger, Receptors, Collagen, Ionomycin, Collagen, Cycloheximide, FAK-related nonkinase, Protein-Tyrosine Kinases, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, PTK2 protein, human, Tetradecanoylphorbol Acetate}, + citation-subset = {AIM, IM}, + completed = {2000-04-07}, + country = {United States}, + issn-linking = {0006-4971}, + issue = {6}, + keywords = {Apoptosis; CD3 Complex, metabolism; Cell Adhesion Molecules, metabolism; Cell Death; Collagen, metabolism; Cycloheximide, pharmacology; DNA Fragmentation; Fas Ligand Protein; Flow Cytometry; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Integrins, metabolism; Ionomycin, pharmacology; Ionophores, pharmacology; Jurkat Cells; Membrane Glycoproteins, metabolism; Plasmids; Protein Synthesis Inhibitors, pharmacology; Protein-Tyrosine Kinases, metabolism; RNA, Messenger, metabolism; Receptors, Collagen; Signal Transduction; T-Lymphocytes, metabolism, pathology; Tetradecanoylphorbol Acetate, pharmacology; Transfection}, + nlm-id = {7603509}, + owner = {NLM}, + pii = {S0006-4971(20)66967-1}, + pmid = {10706873}, + pubmodel = {Print}, + pubstate = {ppublish}, + revised = {2021-02-16}, +} + +@Article{Hemler1990, + author = {Hemler, M. E.}, + journal = {Annual review of immunology}, + title = {VLA proteins in the integrin family: structures, functions, and their role on leukocytes.}, + year = {1990}, + issn = {0732-0582}, + pages = {365--400}, + volume = {8}, + nasa = {90262672}, + chemicals = {Integrins, Receptors, Very Late Antigen}, + citation-subset = {IM, S}, + completed = {1990-07-02}, + country = {United States}, + doi = {10.1146/annurev.iy.08.040190.002053}, + issn-linking = {0732-0582}, + keywords = {Animals; Cell Adhesion; Extracellular Matrix, physiology; Humans; Integrins, biosynthesis, physiology; Leukocytes, physiology; Receptors, Very Late Antigen, biosynthesis, physiology; Structure-Activity Relationship}, + nlm-id = {8309206}, + owner = {NLM}, + pmid = {2188667}, + pubmodel = {Print}, + pubstate = {ppublish}, + references = {212}, + revised = {2021-01-02}, +} + @Comment{jabref-meta: databaseType:bibtex;} @Comment{jabref-meta: grouping: diff --git a/tex/thesis.tex b/tex/thesis.tex index 60eb282..435fdb6 100644 --- a/tex/thesis.tex +++ b/tex/thesis.tex @@ -586,10 +586,12 @@ under close cell-cell contact via \glspl{apc} such as \glspl{dc}, which present peptide-\glspl{mhc} to T cells as well as a variety of other costimulatory signals. These close quarters allow for efficient autocrine/paracrine signaling among the expanding T cells, which secrete gls{il2} and other cytokines to -assist their own growth. Additionally, the lymphoid tissues are comprised of -\gls{ecm} components such as collagen, which provide signals to upregulate -proliferation, cytokine production, and pro-survival pathways\cite{Gendron2003, - Ohtani2008, Boisvert2007, Ben-Horin2004}. +assist their own growth. + +% Additionally, the lymphoid tissues are comprised of +% \gls{ecm} components such as collagen, which provide signals to upregulate +% proliferation, cytokine production, and pro-survival pathways\cite{Gendron2003, +% Ohtani2008, Boisvert2007, Ben-Horin2004}. A variety of solutions have been proposed to make the T cell expansion process more physiological. One strategy is to use modified feeder cell cultures to @@ -629,6 +631,42 @@ cells to interact with the \glspl{mab} relative to beads; this may better emulate the large contact surface area that occurs between T cells and \glspl{dc}. +\subsection*{integrins and T cell signaling} + +Because the microcarriers used in this work are derived from collagen, one key +question is how these collagen domains may interact with the T cells during +culture. This question is further explored in \cref{aim2b}. + +T cells naturally expand in the lymph nodes which have an \gls{ecm} composed of +collagen\cite{Dustin2001, Ebnet1996, Ohtani2008}. Despite this, T cells don't +interact with collagen fibers in the lymph node as the collagen fibers are +sheathed with stromal fibroblasts\cite{Dustin2001, Ebnet1996}. However, the +\gls{ecm} of peripheral tissues is dense with exposed collagen fibers are +available to interact with T cells. Furthermore, T cells have been shown +\invitro{} to crawl along collagen fibers in the presence of \glspl{apc}, +facilitating short encounters with \glspl{apc}\cite{Gunzer2000}. While this may +not be ideal \invivo{} due to the lack of cumulative signal received by +\glspl{apc}\cite{Dustin2001}, it may be advantageous to include collagen domains +\invitro{} as the mode of activation is not specific to any given clone. + +The major surface receptors for collagen are \gls{a2b1} and +\gls{a2b2}\cite{Dustin2001, Hemler1990}. These receptors are not expressed on +naive T cells and thus presence and stimulation of collagen alone is not +sufficient to cause activation or expansion of T cells\cite{Hemler1990}. These +receptors have been shown to lead to a number of functions that may be useful in +the context of T cell expansion. First, they have been shown to act in a +costimulatory manner which leads to increased proliferation\cite{Rao2000}. +Furthermore, \gls{a2b1} and \gls{a2b2} have been shown to protect Jurkat cells +against Fas-mediated apoptosis in the presence of collagen I\cite{Aoudjit2000, + Gendron2003}. Finally, these receptors have been shown to increase \gls{ifng} +production \invitro{} when T cells derived from human \glspl{pbmc} are +stimulated in the presence of collagen I\cite{Boisvert2007}. + +% TODO there are other receptors I could name here that were not explored +% Other integrins that interact with the environment include a4b1, which interacts +% with fibronectin and has been shown to lead to higher IL2 production (Iwata et +% al 2000). + \subsection*{strategies to optimize cell manufacturing} The \gls{dms} system has a number of parameters that can be optimized, and a