AIDSWEEKLY Plus; Monday, May 18, 1998
Daniel J. DeNoon, Senior Editor
Induction of T-cell anergy is thought to be a major process in preventing the immune system from attacking normal self cells. The process also is implicated in the lack of response to several viral and bacterial pathogens.
Such pathogens produce superantigens capable of making the immune system tolerant of non-self antigens. Researchers have discovered that they can use superantigens to experimentally induce anergy, but there has been no way to purify anergic T cells for further study.
Now Curtis C. Maier, Mark I. Greene, and colleagues at the University of Pennsylvania show that CD4(+) T cells rendered anergic by superantigen can be identified by loss of the 6C10 T-cell marker.
"These studies demonstrate that anergic T cells can be purified based on 6C10 expression permitting examination of issues concerning biochemical and biological features specific to T-cell anergy," they wrote.
Maier et al. reported their findings in the journal Proceedings of the National Academy of Sciences ("Unique Molecular Surface Features of In Vivo Tolerized T Cells," PNAS, 1998;95:4499-4503).
The researchers studied T-cell populations in V(beta)8.1 T-cell- receptor (TCR) transgenic mice inoculated with a V(beta)8.1-reactive superantigen dubbed minor lymphocyte-stimulating antigen or Mls-1(a).
They found that lymph-node T cells from the Mls-1(a)-inoculated mice that lacked the 6C10 surface marker were anergic. Stimulation of the TCRs of purified 6C10(-) cells showed that they could neither proliferate nor secrete interleukin 2 (IL-2).
However, 6C10(-) cells from mice not inoculated with Mls-1(a) were not anergic.
"Anergic 6C10(-) T cells from tolerant V(beta)8.1 transgenic mice represent a population of T cells functionally distinct from naive 6C10(-) T cells of normal mice," Maier et al. noted.
An intriguing finding is that the population of anergic CD4(+) T cells contains cells at different levels of differentiation.
"Heterogenous expression of memory markers on 6C10(-) T cells from Mls-1(a) tolerant mice suggests that either maturation or anergic T cells is arrested at various stages after Mls-1(a) stimulation or that the 6C10(-) T cells represent a dynamic population maintained in a nonproliferative state by constant antigenic stimulations," Maier et al. wrote.
The studies open a fascinating window on the behavior of tolerant T cells.
"The regulatory role of anergic cells, if any, remains unclear; nevertheless, their ability to modulate surface receptors involved in homing and other regulatory functions as well as their ability to synthesize cytokines, such as interferon gamma, suggest that anergic cells are not passive bystanders but instead can play an active role in modulating immune responses, possibly by mediating suppressive activities in the periphery," Maier et al. concluded. "The ability to purify anergic T cells from in vivo sources based on loss of 6C10 expression will enable studies on these biological issues as well as biochemical studies on altered TCR-mediated mechanisms."
This work was supported by grants from the National Institutes of Health. Dr. Maier is supported by a postdoctoral fellowship from the National Multiple Sclerosis Society.
The corresponding author for this study is Mark I. Greene, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 252 John Morgan Building, Philadelphia, Pennsylvania 19104-6082. Email: <greene@reo.med.upenn.edu>.
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