THE EFFECT OF TCR V-BETA-8 PEPTIDE PROTECTION AND THERAPY ON T-CELL POPULATIONS ISOLATED FROM THE SPINAL-CORDS OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
Ad. Weinberg et al., THE EFFECT OF TCR V-BETA-8 PEPTIDE PROTECTION AND THERAPY ON T-CELL POPULATIONS ISOLATED FROM THE SPINAL-CORDS OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Journal of neuroimmunology, 49(1-2), 1994, pp. 161-170
Vaccination or treatment of Lewis rats with TCR V beta 8 peptides can
prevent or reverse the clinical signs of experimental autoimmune encep
halomyelitis (EAE) which is mediated predominantly by V beta 8.2(+) CD
4(+)/CD45R lo T cells. However, rats protected or treated with V beta
8 peptides still developed histological lesions in the spinal cord (SC
), even though they remained clinically well. We sought to discern phe
notypic changes characteristic of these SC infiltrating lymphocytes. T
n particular, we focused on whether the immunoregulatory mechanism ind
uced by TCR peptides caused a reduction of V beta 8.2(+) T cells, or i
nduced changes in CD45R lo or hi/CD4(+) subpopulations that have been
associated respectively with EAE induction or recovery. In the V beta
8 peptide vaccinated rats there was a dramatic decrease in the number
of V beta 8.2(+) T cells isolated from the SC early in disease. During
the recovery phase, however, the number of V beta 8.2(+) SC T cells w
as similar in protected and control groups; in contrast, there was a s
triking reduction in the number and size of CD45R hi/CD4(+) T cells in
the protected animals. In rats treated with VP beta 8.2 peptide, no c
hanges were observed in the number of SC V beta 8.2(+) T cells or expr
ession of V beta 8.2 message, but similar to vaccinated rats, there wa
s a marked decrease in the number of CD45R hi/CD4(+) T cells. These da
ta suggest that vaccination with TCR peptides prevented the initial in
flux of encephalitogenic V beta 8.2(+) T cells into the central nervou
s system (CNS), whereas treatment appeared to inactivate V beta 8.2(+)
T cells already present in the CNS. In both cases, TCR peptide-induce
d inhibition of the encephalitogenic T cells apparently preempted the
need for CD45R hi/CD4(+) T cells that may normally be necessary to res
olve the disease.