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Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141
CD8+ T cells use a number of effector mechanisms to
protect the host against infection. We have studied human
CD8+ T cells specific for CMV pp65495–503
epitope, or for staphylococcal enterotoxin B, for the expression
patterns of five cytokines and cytolytic effector molecules before and
after antigenic stimulation. Ex vivo, the cytolytic molecule granzyme B
was detected in a majority of circulating CMV-specific CD8+
T cells, whereas perforin was rarely expressed. Both were highly
expressed after Ag-specific activation accompanied by CD45RO
up-regulation. TNF-
, IFN 
, and IL-2 were sequentially acquired on
recognition of Ag, but surprisingly, only around half of the
CMV-specific CD8+ T cells responded to antigenic stimuli
with production of any cytokine measured. A dominant population
coexpressed TNF- and IFN-, and cells expressing TNF- only,
IFN- only, or all three cytokines together also occurred at lower
but clearly detectable frequencies. Interestingly, perforin expression
and production of IFN- and TNF- in CD8+ T cells
responding to staphylococcal enterotoxin B appeared to be largely
segregated, and no IL-2 was detected in perforin-positive cells.
Together, these data indicate that human CD8+ T cells can
be functionally segregated in vivo and have implications for the
understanding of human CD8+ T cell differentiation and
specialization and regulation of effector
mechanisms.
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