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| Regulation and
function of CD4 T lymphocytes |
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Kim
Bottomly , Ph.D.
Professor of Immunobiology,
Molecular, Cellular, and Developmental Biology,
and Dermatology
Email: kim.bottomly@yale.edu
Room: LH 408
Phone: 785-5391, 785-5396
B.S. University of Washington,
Seattle 1969;
Ph.D. University of Washington 1975 |
The generation of distinct cytokine-producing
CD4 T lymphocyte subsets has been shown to be
influenced by a number of factors including cytokines
present in the priming microenvironment, antigen
presenting cell type, and the amount of priming
antigen. Studies in Dr. Bottomly's laboratory
have shown that Th1/Th2 cell differentiation is
influenced both by the affinity of a peptide antigen
for MHC class II molecules and by the affinity
of the peptide antigen for the T cell receptor,
suggesting that the strength of T cell receptor
mediated signalling is a critical factor in determining
the type of CD4 T effector cell response. These
findings have led to two areas of research. The
first is to understand how the strength of TCR
signalling influences Th2 cell generation. Using
biochemical and genetic approaches, factors influencing
early signalling events required for Th1 and Th2
differentiation are being defined. The second
is to understand how CD4 T lymphocytes and their
associated cytokines regulate the chronic inflammation
disorder that is characteristic of asthma. Using
a newly established model in which Th2 cells and
the local lung environment can be independently
genetically manipulated, the precise function
of factors important in the induction of inflammation
are being determined. Overall, the laboratory
is interested in understanding how appropriate
effector CD4 T cell responses are generated, responses
that lead to effective clearance of pathogens.
Selected Publications
Leitenberg D, Balamuth F, Bottomly K. (2001)
Changes in the T cell receptor macromolecular
signaling complex and membrane microdomains during
T cell development and activation. Semin Immunol.
13(2):129-38
Nikiforow S, Bottomly K, Miller G. (2001) CD4+
T cell effectors inhibit Epstein-Barr virus induced
B cell proliferation. J. Virol. 75(8):3740-52
Welte T, Leitenberg D, Dittel BN, al-Ramadi BK,
Hansen WR, Xie B, Janeway CA Jr. Bothwell AL.
Bottomly K, Fu XY. (1999) The PTK-STAT signaling
pathway has essential roles in T cell activation
in response to antigen simulation. Cold Spring
Harbor Symp. Quant Biol 64:291-302
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