Development of IFN-gamma-producing CD8+ gamma delta+ T lymphocytes and IL-2-producing CD4+ alpha beta+ 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+, gamma delta+ T cell, while proliferation and IL-2 production required the presence of a CD4+, alpha beta+ 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+ 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.
Dieli
F
F
Institute of General Pathology, University of Palermo, ISMEDA-CNR, Italy.
Asherson
G L
GL
Sireci
G
G
Dominici
R
R
Sciré
E
E
Salerno
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000235:genetics; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma