The type 2 pattern of cytokine mRNA produced by BAL cells from SSc patients differs from unopposed IFNgamma production found in healthy BAL cells. This production of type 2 cytokine mRNA by CD8+ T cells is associated with a significant decline in lung function over time, which suggests a pathologic role for these T cells in interstitial fibrosis in SSc.

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Our previous work showed that alternative splicing is used to make an inhibitory variant of human interleukin (IL)-4. Because of homology between IL-4 and IL-2 proteins and receptors, we tested whether alternative splicing is used to generate similar inhibitory variants of human IL-2. Messenger RNA from peripheral blood mononuclear cells was subjected to reverse transcription-polymerase chain reaction using IL-2 exon 1- and exon 4-specific primers. Two amplification products, named IL-2delta2 and IL-2delta3, were found in addition to the native IL-2 product. The IL-2delta2 cDNA sequence was identical to IL-2 cDNA throughout the entire coding region, except exon 2 was omitted by alternative splicing. In IL-2delta3 cDNA, the third exon of IL-2 was omitted by alternative splicing. Unlike IL-2, IL-2delta2 and IL-2delta3 did not stimulate T cell proliferation. However, both inhibited IL-2 costimulation of T cell proliferation, and both inhibited cellular binding of rhIL-2 to high affinity IL-2 receptors. Thus, IL-2 is the second cytokine that uses alternative splicing to generate variants that are competitive inhibitors.