Faculty
Linda Cauley
Assistant Professor of Immunology
lcauley@uchc.edu
Read about Dr. Cauley's research in the
November 6, 2006 issue
of the
UConn Advance
Areas of Interest:
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.
Cauley Publications
Selected Publications:
Zammit, D., Klonowski. K.D. Lefrancois, L., and Cauley, L.S. Residual
antigen presentation after influenza virus infection affects T cell
activation and migration. (submitted for publication).
Zammit, D., Cauley L.S., Pham Q-M and Lefrancois L. 2005. Dendritic
cells maximize the memory CD8 T cell response to infection. Immunity
22:561-570.
Ely, K.H., Cauley, L.S., Roberts, A.D. Brennan, J.W., Cookenham, T.,
and Woodland D.L. 2003. Nonspecific recruitment of memory CD8+ T cells
to the lung airways during respiratory virus infections. J. Immunol.
170:1423-1429.
Cauley, L.S., Cookenham, T., Hogan, R.J., Crowe, S.R., and Woodland.
D.L. 2003. Renewal of peripheral CD8+ memory T cells during secondary
viral infection of antibody sufficient mice. J. Immunol. 170:5597-5606.
Cauley, L.S., Cookenham, T., Miller, T.B., Adams, P.S., Vignali, K.M.,
Vignali, D.A.A. and Woodland. D.L. 2002. Cutting edge: Virus-specific
CD4+ memory T cells in nonlymphoid tissues express a highly activated
phenotype. J. Immunol. 169:6655-6658.
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