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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.
Publications
Selected Publications
Zammit, D., Klonowski. K.D. Lefrançois, 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 Lefrançois 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.
 View more publications, see
Pubmed listing. |
