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ß Is Expressed on Recently Activated Naive and Th1-Like CD4 Cells but Is Down-Regulated by IL-4 During Th2 Differentiation1
Divisions of
*
Immunochemistry and
Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
Lymphotoxin (LT) is a cytokine that orchestrates lymphoid
neogenesis and formation of germinal center reactions. LT exists as a
membrane heterotrimer of 
and ß subunits and is secreted as a
homotrimer, LT3. Using LTßR.Fc, expression of LTß on CD4 T
cell subsets was investigated in a TCR transgenic model. LTß was
evident 24–72 h after activation of naive T cells with specific Ag,
and declined thereafter. Early expression was independent of IFN-
and IL-12, however, IL-12 prolonged expression. LTß was reinduced
within 2–4 h after Ag restimulation, but declined by 24 h
regardless of IL-12 or IFN- priming. Exposure of naive T cells to
IL-4 did not affect early LTß expression at 24 h, but
resulted in subsequent down-regulation. IL-4-differentiated Th2
effectors did not re-express LTß, and LTß was transiently
found on Th1 clones but not Th2 clones. LT3 and TNF were
immunoprecipitated from supernatants and lysates of IL-12 primed cells
but not IL-4 primed cells. These studies demonstrate that LTß is
expressed by activated naive CD4 cells, unpolarized IL-2-secreting
effectors, and Th1 effectors. In contrast, loss of surface LTß and
a lack of LT3 and TNF secretion is associated with prior exposure to
IL-4 and a Th2 phenotype.
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