Linda S. Cauley, Ph.D.Associate Professor of Immunology
|B.S.||University of Keele||Biology and Geography|
|Ph.D.||University of Oxford||Molecular Medicine|
|Ph.D. Studentship||University of Oxford|
|Postdoctoral||The Scripps Research Institute, Department of Immunology||Assembly of Class I MHC Molecules|
|Name of Award/Honor||Awarding Organization|
|Junior Faculty Travel Award||FASEB|
|Junior Faculty Travel Award||FASEB|
|Junior Faculty Travel Award||FASEB|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|Graduate Student Admissions committee||Education Committee||Reviewer||UConn Health||University||2019||2021|
|Allergy, Immunology and transplantation||Study Section||member||External||National||2018||2024|
|Graduate Program Review - University of Miami||Advisory Committee||Reviewer||External||National||2018||2018|
|Education council||Education Committee||member||UConn Health||University||2017||2019|
|Merit review committee||Research Committee||member||UConn Health||University||2017||2019|
|Immunology Graduate program||Education Committee||Director||University||2017||2018|
|Immunology graduate program||Education Committee||Associate Director||UConn Health||University||2014||2017|
|NIH study section: ZGM1 TWD-A (CB) COBRE multiple project grants||Study Section||Member||External||National||2012|
|NIH Special Emphasis Panel: ZAI1-QV-I-M1. Immunobiology of Host Defense PO1 grants||Study Section||Member||External||National||2012|
|NIH Special emphasis panel: ZAI1-RRS-I-J1- Integrated Immune Control of Virus Infection||Study Section||Member||External||National||2010|
|NIH study section: ZAI1 EB-A (M1) - Basic HIV Vaccine Discovery Program||Study Section||Member||External||National||2010|
|Student Affairs Committee||Advisory Committee||Member||UConn Health||University||2010||2012|
|NIH Study section: ZAI1 BDP-I (J3) - Immune Mechanisms of Virus Control||Study Section||Member||External||National||2009|
|NIH Study section: - ZAI1 EL-M (J1) Integrated Immune Control of Virus Infection||Study Section||Member||External||National||2009|
|NIH Study section: HIV Vaccine Discovery Research||Study Section||Member||External||National||2009|
|ZRG1 IDM-C- Challenge grants.||Other||reviewer||External||National||2009|
|American Heart Association Study Section, Immunology and Virology||Study Section||Member||External||National||2008|
|Federation of American Societies for Experimental Biology||Professional/Scientific Organization||Symposium chair||External||National||2008|
|NIH Study section: (U19) ZAI1 KS-I (J3) - “Cooperative Centers for Translational Research on Human Immunology and Biodefense.||Study Section||Member||External||National||2008|
|Graduate Student Admissions Committee||Education Committee||Member||UConn Health||University||2008||2012|
|University of Connecticut Graduate Program Admissions Committee||Editorial Board||Member||UConn Health||University||2007||2010|
|American Heart Association Study Section, Immunology and Microbiology II.||Study Section||Member||External||National||2007||2010|
|NIH New Investigator Workshop||Professional/Scientific Organization||Member||External||National||2007|
|British Medical Research Council Grant.||Professional/Scientific Organization||Mail reviewer||External||International|
|UCONN Immunology Graduate Program||Education Committee||Member||UConn Health||University|
|Doctoral thesis, Alex Chen - University of Massachusetts||Education Committee||External Examiner||External||University|
|Doctoral thesis Ching Tsai, The Geisel School of Medicine at Dartmouth||Education Committee||External Examiner||External||University|
|The Journal of Experimental Medicine; The Journal of Immunology; The European Journal of Immunology; Immunology Letters; PLoS One; PLoS Pathogens; Cell Host and Microbe; Immunity. J. Leuk. Biol.; J. Immunol. Methods||Professional/Scientific Journal||Ad Hoc reviewer||External||National|
|American Association of Immunology||Professional/Scientific Organization||Member||External||National|
The major focus of my lab is to investigate the mechanisms that control protective immunity to influenza and other respiratory virus infections. These pathogens are a major cause of human mortality every year. Cytotoxic T cells (CTL) play an important role in viral clearance and can provide short-term heterosubtypic immunity, indicating that they could be an effective target for vaccination. Unfortunately, cellular immunity to viral infections lasts only a few months even when large self-renewing populations of virus-specific memory CD8 T cells have been established. An important goal of my lab is to determine why protective cellular immunity declines so rapidly and why circulating memory T cells become ineffective at accelerating viral clearance during secondary challenge. Better understanding of the mechanisms that regulate T cell responses in vivo are likely to lead to more effective methods of vaccination against viruses and other pathogens that invade the respiratory tract. Transgenic mice, recombinant strains of influenza virus and MHC class I tetramer technology will be used to track CD4 and CD8 T cell response in vivo by flow cytometry and confocal microscopy. Influenza virus infection is largely limited to the respiratory tract, enabling us to analyze the local effects of a tissue-specific infection.
In a recent study, we showed that processed T cell antigens persist near the site of virus amplification in the lungs and draining lymph node for at least two months after influenza virus infection (Zammit et al.). Our data show that these processed T cell antigens have a profound influence on local T cell migration and activation in the lungs. Ongoing studies will investigate the effects of residual antigen presentation on memory T cells responses in vivo after influenza and other viral infections. These studies will include analysis of the antigen presentation pathways that are used during the different stages of the response. The effects of residual antigen presentation on adhesion molecules and other inflammatory mediators that influence local T cell migration will also be analyzed. Evidence suggests that T cell activation and location at the time of secondary viral challenge are likely to be important factors in protection. We will therefore investigate whether residual antigen presentation is an essential component of protective immunity.
Another long-term goal of my lab is to investigate how antibody responses influence, and potentially interfere with, T cell responses in immune animals. Preliminary data show that repeated pulmonary challenge with the same respiratory virus leads to extensive proliferation by virus-specific CD8 T cells in the draining lymph nodes, but little or no T cell response or local inflammation in the lungs. This study will investigate whether neutralizing antibodies redirect antigen presentation in the lungs to a pathway that is suppressive for T cell activation.
Not accepting lab rotation students at this time
CTLs Get SMAD When Pathogens Tell Them Where to Go.
Journal of immunology (Baltimore, Md. : 1950) 2022 Sep;209(6):1025-1032
SMAD4 and TGFβ are architects of inverse genetic programs during fate determination of antiviral CTLs.
eLife 2022 Aug;11
Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses.
The Journal of experimental medicine 2020 Aug;217(8):
Immunity to Respiratory Infection Is Reinforced Through Early Proliferation of Lymphoid TRM Cells and Prompt Arrival of Effector CD8 T Cells in the Lungs.
Frontiers in immunology 2019 Jan;101370
Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.
Journal of immunology (Baltimore, Md. : 1950) 2015 Nov;196124-34
Smad4 promotes differentiation of effector and circulating memory CD8 T cells but is dispensable for tissue-resident memory CD8 T cells.
Journal of immunology (Baltimore, Md. : 1950) 2015 Jan;194(5):2407-14
Why is coinfection with influenza virus and bacteria so difficult to control?
Discovery medicine 2015 Jan;19(102):33-40
CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection.
Immunity 2014 Oct;41(4):633-45
Oral infection drives a distinct population of intestinal resident memory CD8(+) T cells with enhanced protective function.
Immunity 2014 Apr;40(5):747-57
Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection.
Journal of leukocyte biology 2013 Sep;95(2):215-24
Antigen and transforming growth factor Beta receptors contribute to long term functional and phenotypic heterogeneity of memory CD8 T cells.
Frontiers in immunology 2013 Jan;4227
Guarding the perimeter: protection of the mucosa by tissue-resident memory T cells.
Mucosal immunology 2013 Jan;6(1):14-23
Division of labor between subsets of lymph node dendritic cells determines the specificity of the CD8⁺ T-cell recall response to influenza infection.
European journal of immunology 2011 Sep;41(9):2632-41
Duration of antigen availability influences the expansion and memory differentiation of T cells.
Journal of immunology (Baltimore, Md. : 1950) 2011 Sep;187(5):2310-21
Environmental and antigen receptor-derived signals support sustained surveillance of the lungs by pathogen-specific cytotoxic T lymphocytes.
Journal of virology 2011 May;85(9):4085-94
The migration of T cells in response to influenza virus is altered in neonatal mice.
Journal of immunology (Baltimore, Md. : 1950) 2010 Sep;185(5):2980-8
In situ imaging reveals different responses by naïve and memory CD8 T cells to late antigen presentation by lymph node DC after influenza virus infection.
European journal of immunology 2008 Dec;38(12):3304-15
Persistent antigen presentation after acute vesicular stomatitis virus infection.
Journal of virology 2007 Feb;81(4):2039-46
Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs.
Immunity 2006 Oct;25(4):643-54
Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration.
Immunity 2006 Apr;24(4):439-49
Dendritic cells maximize the memory CD8 T cell response to infection.
Immunity 2005 May;22(5):561-70
Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo.
Journal of immunology (Baltimore, Md. : 1950) 2004 May;172(9):5450-5
Activated primary and memory CD8 T cells migrate to nonlymphoid tissues regardless of site of activation or tissue of origin.
Journal of immunology (Baltimore, Md. : 1950) 2004 Apr;172(8):4875-82
Renewal of peripheral CD8+ memory T cells during secondary viral infection of antibody-sufficient mice.
Journal of immunology (Baltimore, Md. : 1950) 2003 Jun;170(11):5597-606
Nonspecific recruitment of memory CD8+ T cells to the lung airways during respiratory virus infections.
Journal of immunology (Baltimore, Md. : 1950) 2003 Feb;170(3):1423-9
Cutting edge: virus-specific CD4+ memory T cells in nonlymphoid tissues express a highly activated phenotype.
Journal of immunology (Baltimore, Md. : 1950) 2002 Dec;169(12):6655-8
Long-term maintenance of virus-specific effector memory CD8+ T cells in the lung airways depends on proliferation.
Journal of immunology (Baltimore, Md. : 1950) 2002 Nov;169(9):4976-81
Antiviral memory T-cell responses in the lung.
Microbes and infection / Institut Pasteur 2002 Aug;4(10):1091-8
Memory T-cells in non-lymphoid tissues
Curr. Opin. Investig. Drugs. 2002 Jan;333-36
Superantigen-induced CD4 T cell tolerance mediated by myeloid cells and IFN-gamma.
Journal of immunology (Baltimore, Md. : 1950) 2000 Dec;165(11):6056-66
Transferable anergy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8- cells and interferon gamma.
The Journal of experimental medicine 1997 Jul;186(1):71-81
Evidence for an early heavy chain intermediate in the assembly of H-2Db class I MHC molecules.
Molecular immunology 1995 Feb;32(2):137-46
Assembly of MHC class I molecules analyzed in vitro.
Cell 1990 Jul;62(2):285-95
Resistance to H-2-restricted but not to allo-H2-specific graft and cytotoxic T lymphocyte responses in lymphoma mutant.
Journal of immunology (Baltimore, Md. : 1950) 1990 Jul;145(1):52-8
Association of class I major histocompatibility heavy and light chains induced by viral peptides.
Nature 1989 Aug;340(6233):443-8
Allelic variation in the DR subregion of the human major histocompatibility complex.
Proceedings of the National Academy of Sciences of the United States of America 1987 Sep;84(17):6234-8
Molecular mapping class II polymorphisms in the human major histocompatibility complex. II. DQ beta.
Journal of immunology (Baltimore, Md. : 1950) 1987 Jul;139(2):574-86
Molecular mapping of class II polymorphisms in the human major histocompatibility complex. I. DR beta.
Journal of immunology (Baltimore, Md. : 1950) 1987 Jul;139(2):562-73
The EB virus genome in Daudi Burkitt's lymphoma cells has a deletion similar to that observed in a non-transforming strain (P3HR-1) of the virus.
The EMBO journal 1984 Apr;3(4):813-21
Environmental cues orchestrate regional immune surveillance and protection by pulmonary CTLs.
Journal of leukocyte biology 2016 Jun;100905-912
Antigen keeps the local lymph nodes reactive after viral infection
Current Trends in Immunology 2008 Jan;961-66