Detalles del proyecto
Description
The objectives of this research are to elucidate the mechanism of cell
killing by cytotoxic T lymphocytes (CTL), an important phenomenon in
cellular immunology. The specific aims are: (1) to observe microscopically
the dynamic morphological changes of CTL and target cells following
controled onset of conjugation of a pair of single cells; (2) to determine
the biophysical properties of CTL and target cells on a single-cell basis
and their interaction during killing; and (3) to assess the effects of
biochemical and immunochemical modifications on the biophysical properties
of CTL and their correlation with the killing process. The experiments
will be performed on two types of cell systems: (1) a human cytolytic
T-cell line (F1) with JY (HLA-A2[unreadable]+[unreadable], -B7[unreadable]+[unreadable], DR4,6[unreadable]+[unreadable]) B-lymphoblastoid
cell lines as target cells, and (2) a mouse cytotoxic T-lymphocyte
hybridoma with EL4 cells as target cells. The biophysical properties of
the CTLs and their specific target cells will be determined individually
and also during their interaction in the killing process. These tests will
be made by using the micropipette aspiration technique already established
in our laboratory for investigations on various types of blood cells
including T lymphocytes. With the aid of a video recording and analysis
system and computer assistance, the viscoelsstic properties of these cells
will be derived from their deformational behavior in response to an
aspiration pressure applied via the micropipette. By using two
micropipettes, one to hold a CTL and the other a target cell, these cells
will be brought into contact, thus controlling the time of onset for
conjugation. Subsequent measurements will provide dynamic information on
the biophysical states of both cells throughout the course of the various
phases of the killing process. The energy of interaction between the two
cells will be estimated from the forces required to separate them. These
biophysical measurements will also be made following several types of
treatments to modify the properties of the CTL and/or target cells,
including the blockade of cytotoxicity by using monoclonal antibodies,
modifications of cell surface charge, ionic environment, cytoskeletal
apparatus and lipid composition, variations in temperature, and induction
of membrane capping. Correlation of the results of these biophysical
studies with the biochemical events studied by other investigators will
serve to increase our understanding of the chemico-mechanical transduction
process in cell killing by cytotoxic T lymphocytes. (LB)
Estado | Finalizado |
---|---|
Fecha de inicio/Fecha fin | 6/1/85 → 1/1/90 |
Financiación
- National Cancer Institute
Keywords
- Biofísica
- Biología celular
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