Nuclear Medicine Technology and Other
Health Applications
Project Title: Lymphocytopoiesis and Transplantation Immunology
14.
Scope:
(Cont'd)
the changes during depletion and repletion, and the changes
of allograft immunization.
RX-O01-03-(d)_
in the course
Labeling of thymocytes with tritiated thymidine via intra-arterial
cannulae which has provided much information about the pattern and
magnitude of T cell migration in calves will be used to gain more
information on the fate and iife span of T cell migrants.
The magnitude
of migration from the thymus is studied also by observing the natural
marker of T cells, the alloantigen 8..
mouse 9 + T cells
The large postnatal migration of
to the intestinal lymphoid tissues has been correlated
with postnatal population of gut by bacteria, suggesting that the migratory stimulus may be from bacterial antigens.
This will be investigated
by studying T cell migration into the Peyer's patches and gut lumen using
sterile and contaminated exteriorized intestinal loops.
The long term study of tritiated thymidine labeled DNA and cell
turnover is complicated by the fact that the tritiated thymidine is
reutilized.
However, in tne lymph node there appears to be either no
reutilization or reutilization is at the polynucleotide level thereby
escaping destruction by thymidine kinase.
A possible method for studying
this question is regional lymph node perfusion.
Infusion of DNA pre-
cursors into the lymph node would label only those cells in DNA synthesis
within the lymph node and cells entering the node from other lymphoid
organs would not be labeled,
Celis leaving the lymph node can be monitored
constantly by cannulating the efferent lymphatic duct.
Effective prolongation of kidney allograft survival was obtained
with pre- and post-grafting ECIB in some goats. However, for unknown
reasons some kidneys were rejected normally. Effective immunosuppression
by ECIB may depend upon the degree of histocompatibility between donor and
recipient. Methods for determining the "closeness" of match between donors
and recipients using the one way mixed leukocyte reaction and leukocyte
typing will be applied.
For ultimate clinical application it appears that
ECIB, ECIL, or both, will have to be used in conjunction with drug
immunosuppressive therapy.
The effectiveness of ECIB and ECIL would be
greatly enhanced if more lymphocytes could be mobilized from tissue
and killed in transit through the blood.
ECIB has been applied in patients
ronic lymphocytic leukemia (CLL) with beneficial effects.
i
life?
As
Wh need treatment these studies will continue with the objective
ining effect on longevity, morbidity, and duration of useful
IB has no harmful effects in contrast to chemotherapeutic drugs
that produce severe and sometimes fatal thrombopenia, granulocytopenia,
anemia, and immunosuppression.
An adequate evaluation will require at
least 10-15 years and a continual flow of patients.
(See Continuation Sheet)
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