REGULATION OF BASIC PROTEIN SPECIFIC T LYMPHOCYTE LINES

Experimental autoimmune encephalomyelitis (EAE) involves a
pathological process which causes CNS inflammatory lesions,
demyelination, and overt clinical signs. The chronic or relapsing
form of EAE mimics in many ways the human disease, multiple
sclerosis. Many of the processes which have been studied in EAE
may have direct application to eventual therapies and prophylaxis
in MS and other human demyelinating diseases. The overall goal
of this proposal is to describe mechanisms which regulate the
activity of encephalitogenic T lymphocyte lines. The BP-1 T
lymphocyte line has been selected for its ability to recognize and
respond to myelin basic protein. The BP-1 line acquired the
capability to induce clinical EAE and DTH reactions to BP in
recipient rats only after activation with BP presented by
histocompatible accessory cells. Furthermore, injection of
irradiated, activated BP-1 cells induced resistance to active EAE
produced by injection of BP in CFA. The maturation from resting
to fully activated T effector cells thus represents a crucial stage
in the development of clinical EAE as well as protection against
EAE. Aim 1) To evaluate the ability of accessory cells from thymus,
spleen, lymph nodes, peritoneum, and brain capillary endothelium
to activate encephalitogenic T lymphocytes, and to characterize
the activation sequence. Aim 2) To determine if immunologic recognition of activated BP-
1 cells is associated with protection against actively induced EAE. This proposal will study the interactions between the T cells that
mediate EAE and the antigen presenting cells which control the
activation and migration of the T cells into the tissue. This
interaction may be critical in the maintenance of nonresponse to
self as well as the inflammation which results in EAE. Thus,
information from this research may contribute significantly to the
regulation of inflammatory processes in the CNS and perhaps in
other tissues as well.