Development of IFN- gamma -producing CD8 super(+) gamma delta super(+) T lymphocytes and IL-2-producing CD4 super(+) alpha beta super(+) T lymphocytes during contact sensitivity

This paper describes the development of Ag-specific proliferation and the production of IFN- gamma and IL-2 during contact sensitivity (CS) to the hapten picryl chloride (PCl). Lymph node cells from mice immunized with PCl proliferate and produce IFN- gamma and IL-2 when re-exposed to the specific Ag in vitro. Time course experiments showed that the peak IFN- gamma production occurred at days 3 and 4 after immunization, with a sharp decline by day 6. In contrast, proliferation and IL-2 production peaked at day 3 but persisted up to day 10. Proliferation and IFN- gamma and IL-2 production displayed by immune lymph node cells were Ag-specific but required different cell populations. In fact, the production of IFN- gamma was due to a CD8 super(+), gamma delta super(+) T cell, while proliferation and IL-2 production required the presence of a CD4 super(+), alpha beta super(+) T cell. Furthermore, IFN- gamma production showed genetic (MHC) restriction, and finer analysis using congenic strains of mice indicated that the K molecule was the restricting element. This was confirmed by blocking the K molecule of the APC used to trigger IFN- gamma production with a specific mAb. In contrast, proliferation and IL-2 production were I-A-restricted, as demonstrated using congenic strains of mice and blocking the I-A molecule of the APCs. Further analysis using purified gamma delta super(+) cells revealed that these cells produced IFN- gamma in an Ag-specific and MHC (K)-restricted fashion. Injection of mice with a mAb to IL-2 blocked subsequent in vitro proliferation, as well as IL-2 and IFN- gamma production, while all three in vitro responses were unaffected by injection of a mAb to IFN- gamma given at the time of immunization. Furthermore, injection of mice with a mAb to IL-2 blocked the CS reaction when given at the time of immunization, while it had no effect when given at the time of challenge. Injection of mice with mAb to IFN- gamma at the time of challenge reduced but did not abolished CS, suggesting that IFN- gamma is important but not exclusively responsible for the CS reaction.