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*
Queensland Institute of Medical Research, Brisbane, Queensland, Australia;
Joint Experimental Oncology Program, Brisbane, Queensland, Australia;
Joint Transplantation Biology Program and Cooperative Research Centre for Vaccine Technology, Brisbane, Queensland, Australia; and
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599
Immune deviation of cytolytic T cell function, induced by type 2
cytokines like IL-4, is an attractive concept to explain failure of the
immune system in some diseases. However, this concept is challenged by
previous conflicting results on whether type 2 cytokine-producing
CD8+ T cells are cytolytic. Therefore, we have analyzed the
relationship between cytolytic activity and cytokine production among
large numbers of primary CD8+ T cell clones. Single murine
CD8+ T cells of naive phenotype were activated at high
efficiency with immobilized Abs to CD3, CD8, and CD11a in the presence
of IL-2 (neutral conditions) or IL-2, IL-4, and anti-IFN-
Ab (type 2-polarizing conditions) for 8–9 days. Under neutral
conditions, most clones produced IFN- without IL-4 and were
cytolytic. Under type 2-polarizing conditions, most clones produced
IFN- and IL-4 but displayed variable cytolytic activity and CD8
expression. Separation on the basis of surface CD8 levels revealed
that, compared with CD8high cells from the same cultures,
CD8low cells were poorly cytolytic and expressed low levels
of perforin mRNA and protein and granzyme A, B, and C mRNA. A similar,
smaller population of noncytolytic CD8low cells was
identified among CD8+ T cells activated in mixed lymphocyte
reaction with IL-4. Variable efficiency of generation of the
noncytolytic cells may account for the differing results of earlier
studies. We conclude that IL-4 promotes the development of a
noncytolytic CD8low T cell phenotype that might be
important in tumor- or pathogen-induced immune
deviation.
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