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The Journal of Immunology, Vol 156, Issue 1 153-159, Copyright © 1996 by American Association of Immunologists
ARTICLES |
NS Williams and VH Engelhard
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Although cytotoxic activity has generally been shown to reside in the CD8+ population of T lymphocytes, there are numerous examples of cytotoxic CD4+ T cells. In the present study, we found that after depletion of CD8+ T cells, CD4+ T cells cultured in short-term in vitro mixed lymphocyte cultures developed strong Ag-specific cytotoxic activity. Such CD4+ CTL lysed both Fas+ and Fas- target cells and developed in Fas ligand-deficient gld mice. Thus, in contrast to several recent reports involving long-term T cell clones or short-term mitogen-activated splenocytes, the cytotoxic activity of these CD4+ CTL is not dependent on Fas-Fas ligand interactions. However, CD4+ cells derived in a similar manner from perforin knockout mice showed greatly decreased target cell lysis, indicating that their cytotoxic activity is primarily dependent on a perforin-based mechanism. The Fas-Fas ligand pathway has been shown to be important in the maintenance of peripheral tolerance, but to have a minimal role in protection against viral and bacterial pathogens. Thus, the existence of a population of CD4+ CTL that utilizes perforin re-emphasizes the likely importance of these cells in a classical defensive role against foreign pathogens, in addition to their already implied role as modulators of the immune response.
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