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Age-Associated Rapid and Stat6-Independent IL-4 Production by NK1^-CD4⁺8^- Thymus T Lymphocytes¹

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China; and Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

The source of IL-4 required for priming naive T cells into IL-4-secreting effectors has not been clearly identified. Here we show that upon TCR stimulation, thymus NK1^-CD4⁺8^- T cells produced IL-4, the magnitude of which was inversely correlated with age. This IL-4 production response by Th2-prone BALB/c mice was 9-fold that of Th1-prone C57BL/10 mice. More than 90% of activated NK1^-CD4⁺8^- thymocytes did not use the invariant V14-J281 chain characteristic of typical CD1-restricted NK1⁺CD4⁺ T cells. Stat6-null NK1^-CD4⁺8^- thymocytes produced bioactive IL-4, with induction of IL-4 mRNA expression within 1 h of stimulation. Our results support the possibility that TCR repertoire-diverse conventional NK1^-CD4⁺ T cells are a potential IL-4 source for directing naive T cells toward Th2/type 2 CD8⁺ T cell (Tc2) effector development.

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