Abstract

Interleukin 13 is a Th2 type (anti-inflammatory) cytokine produced by activated T cells. We have cloned a naturally occurring mRNA splice variant of IL-13 in which the second exon is omitted (termed δE2). We have developed RT-PCR assays for quantitation and discrimination of δE2/IL-13 gene expression, and cloned each of the molecules as HIS-tagged proteins for use in in vivo and in vitro studies.

We find that unlike IL-13, δE2 is expressed predominantly under Th1 conditions: δE2 is expressed by spleen cells stimulated with polyclonal activators and in the lymph nodes of mice immunized with CFA as adjuvant. Addition of exogenous δE2 to cultured antigen presenting cells induces phenotypic changes characteristic of an inflammatory (Th1) response, such as increased inflammatory cytokine secretion (TNF-α and IL-12). Addition of exogenous δE2 to antigen specific T cell cultures results in an increase in TNF-α producing cells as determined by ELIspot. Treatment of mice with exogenous δE2 at the time of immunization with CFA and antigen results in significant increases in the expression of inflammatory genes, including IL-12, CD28, and CD5. Lastly, we find that this splice variant is produced primarily by activated (CD19+, CD86+) B cells

Given the expression pattern of δE2 and its ability to modulate the expression of inflammatory cytokines, we hypothesis that δE2 is a unique cytokine involved in inflammatory immune responses

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