DEVELOPMENT OF IFN-GAMMA-PRODUCING CD8(-DELTA(+) T-LYMPHOCYTES AND IL-2-PRODUCING CD4(+) ALPHA-BETA(+) T-LYMPHOCYTES DURING CONTACT SENSITIVITY() GAMMA)

This paper describes the development of Ag-specific proliferation and the production of IFN-gamma and IL-2 during contact sensitivity (CS) t o the hapten picryl chloride (PCI). Lymph node cells from mice immuniz ed with PCI 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 pr oduction peaked at day 3 but persisted up to day 10. Proliferation and IFN-gamma and IL-2 production displayed by immune lymph node cells we re Ag-specific but required different cell populations. In fact, the p roduction of IFN-gamma was due to a CD8(+), gamma delta(+) T cell, whi le proliferation and IL-2 production required the presence of a CD4(+) , alpha beta(+) T cell. Furthermore, IFN-gamma production showed genet ic (MHC) restriction, and finer analysis using congenic strains of mic e indicated that the K molecule was the restricting element. This was confirmed by blocking the K molecule of the APC used to trigger IFN-ga mma production with a specific mAb. In contrast, proliferation and IL- 2 production were I-A-restricted, as demonstrated using congenic strai ns of mice and blocking the I-A molecule of the APCs. Further analysis using purified gamma delta(+) cells revealed that these cells produce d IFN-gamma in an Ag-specific and MHC (K)-restricted fashion. Injectio n 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 r esponses were unaffected by injection of a mAb to IFN-gamma given at t he time of immunization. Furthermore, injection of mice with a mAb to IL-2 blocked the CS reaction when given at the time of immunization, w hile it had no effect when given at the time of challenge. Injection o f 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 exclu sively responsible for the CS reaction.