NDLI: Design, Assessment, and in vivo Evaluation of a Computational Model Illustrating the Role of CAV1 in CD4+ T-lymphocytes

Content Provider	PubMed Central
Author	Conroy, Brittany D. Herek, Tyler A. Shew, Timothy D. Latner, Matthew Larson, Joshua J. Allen, Laura Davis, Paul H. Helikar, Tomáš Cutucache, Christine E.
Copyright Year	2014
Abstract	Caveolin-1 (CAV1) is a vital scaffold protein heterogeneously expressed in both healthy and malignant tissue. We focus on the role of CAV1 when overexpressed in T-cell leukemia. Previously, we have shown that CAV1 is involved in cell-to-cell communication, cellular proliferation, and immune synapse formation; however, the molecular mechanisms have not been elucidated. We hypothesize that the role of CAV1 in immune synapse formation contributes to immune regulation during leukemic progression, thereby warranting studies of the role of CAV1 in CD4+ T-cells in relation to antigen-presenting cells. To address this need, we developed a computational model of a CD4+ immune effector T-cell to mimic cellular dynamics and molecular signaling under healthy and immunocompromised conditions (i.e., leukemic conditions). Using the Cell Collective computational modeling software, the CD4+ T-cell model was constructed and simulated under CAV1 +/+, CAV1 +/−, and CAV1 −/− conditions to produce a hypothetical immune response. This model allowed us to predict and examine the heterogeneous effects and mechanisms of CAV1 in silico. Experimental results indicate a signature of molecules involved in cellular proliferation, cell survival, and cytoskeletal rearrangement that were highly affected by CAV1 knock out. With this comprehensive model of a CD4+ T-cell, we then validated in vivo protein expression levels. Based on this study, we modeled a CD4+ T-cell, manipulated gene expression in immunocompromised versus competent settings, validated these manipulations in an in vivo murine model, and corroborated acute T-cell leukemia gene expression profiles in human beings. Moreover, we can model an immunocompetent versus an immunocompromised microenvironment to better understand how signaling is regulated in patients with leukemia.
Related Links	http://dx.doi.org/10.3389/fimmu.2014.00599
Starting Page	599
File Format	PDF
ISSN	16643224
e-ISSN	16643224
Journal	Frontiers in Immunology
Volume Number	5
Language	English
Publisher	Frontiers Media S.A.
Publisher Date	2014-12-01
Access Restriction	Open
Rights Holder	Frontiers Media S.A.
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Design, Assessment, and in vivo Evaluation of a Computational Model Illustrating the Role of CAV1 in CD4+ T-lymphocytes

NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells

Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment

A novel role for IL-27 in mediating the survival of activated mouse CD4 T lymphocytes

Ex Vivo Restimulation of Human PBMC Expands a CD3+CD4−CD8− γδ + T Cell Population That Can Confound the Evaluation of CD4 and CD8 T Cell Responses to Vaccination

In vivo suppression of naïve CD4 T-cell responses by IL-2 and antigen stimulated T-lymphocytes in the absence of APC competition

Jacalin: a lectin mitogenic for human CD4 T lymphocytes.

Emerging Roles of L-Type Voltage-Gated and Other Calcium Channels in T Lymphocytes

Unbiased transcriptomes of resting human CD4+CD45RO+ T lymphocytes

Design, Assessment, and in vivo Evaluation of a Computational Model Illustrating the Role of CAV1 in CD4+ T-lymphocytes

Similar Documents

Design, Assessment, and in vivo Evaluation of a Computational Model Illustrating the Role of CAV1 in CD4+ T-lymphocytes

NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells

Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment

A novel role for IL-27 in mediating the survival of activated mouse CD4 T lymphocytes

Ex Vivo Restimulation of Human PBMC Expands a CD3+CD4−CD8− γδ + T Cell Population That Can Confound the Evaluation of CD4 and CD8 T Cell Responses to Vaccination

In vivo suppression of naïve CD4 T-cell responses by IL-2 and antigen stimulated T-lymphocytes in the absence of APC competition

Jacalin: a lectin mitogenic for human CD4 T lymphocytes.

Emerging Roles of L-Type Voltage-Gated and Other Calcium Channels in T Lymphocytes

Unbiased transcriptomes of resting human CD4+CD45RO+ T lymphocytes

Design, Assessment, and in vivo Evaluation of a Computational Model Illustrating the Role of CAV1 in CD4+ T-lymphocytes