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* Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, United Kingdom
Ag-specific Th1 and Th2 cytokine-producing CD4 T cells were
quantitated in secondary lymphoid and tertiary tissues following oral
Listeria monocytogenes infection. Although the response
to Listeria was previously believed to be predominately
Th1 like, CD4 T cells producing IL-4 or IL-5 comprised a substantial
proportion of the overall primary and memory response. The frequency of
IFN-
-, IL-4-, or IL-5-producing primary effector or memory CD4 T
cells was significantly higher in lung, liver, and intestinal lamina
propria (LP) as compared with spleen and lymph node. However, maximum
numbers of IL-4- and IL-5-producing cells were detected in the LP
several days after the peak of the Th1 response, and IL-5 production
was skewed toward the mucosal tissues. Remarkably, the recall response
resulted in sustained Th1 and Th2 responses in tertiary, but not
lymphoid tissues and long-term retention of Th1 and Th2 memory cells in
equal proportions in the LP. Finally, CD40 ligand was essential for
induction of IFN- in the spleen and LP, but not in the liver and
lung, while the IL-4 response required CD40 ligand only in the spleen.
Therefore, the rules governing the effector phenotype, and the overall
magnitude of the CD4 response, are regulated at the level of individual
tissues.
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