IL-4 from Th2-type cells suppresses induction of delayed-type hypersensitivity elicited shortly after immunization

• Published in: Immunology and cell biology Vol. 81; no. 6; pp. 424 - 430
• Main Authors: Jacysyn, Jacqueline F, Abrahamsohn, Ises A, Macedo, Mahasti S
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2003; Blackwell Science Ltd
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Cells, Cultured; delayed‐type hypersensitivity; Female; Hypersensitivity, Delayed - immunology; Hypersensitivity, Delayed - therapy; IL‐4; Immunization; Interleukin-10 - antagonists & inhibitors; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - physiology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Inbred DBA; Ovalbumin - administration & dosage; Ovalbumin - immunology; Th2 cells; Th2 Cells - immunology; Th2 Cells - transplantation
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1046/j.1440-1711.2003.01194.x

The pure delayed‐type hypersensitivity reaction obtained in 4‐day ovalbumin‐sensitized mice after antigen challenge in the footpad was abrogated by transfer of in vitro expanded, antigen‐specific lymphoblasts derived from ovalbumin‐hyperimmunized donors (high antibody producers), 12 h before immunization. This effect was specific inasmuch as Trypanosoma cruzi‐specific blasts derived from Tc‐Ag‐hyperimmunized mice did not inhibit delayed‐type hypersensitivity in ovalbumin‐immunized recipients. The ovalbumin‐specific blasts displayed a Th2 cytokine profile, secreting IL‐4 and IL‐10 upon restimulation in vitro with ovalbumin, but not IFN‐γ or IL‐2. In addition, recipients of such cells produced much more IgG1 and IgE antibodies. When the frequency of T‐cell blasts was enriched among these cells, transfer of four million cells was enough to prevent the induction of delayed‐type hypersensitivity. Neutralization of IL‐4 alone just before cell transfer not only restored the delayed‐type hypersensitivity reaction, but also maintained it in a plateau for at least 72 h after challenge. Recipients treated in this way also showed a shift back towards a Th1 phenotype, indicated by the increase in IL‐2, IFN‐γ and IL‐12 synthesis. No synergistic action was observed when IL‐4 and IL‐10 were concomitantly neutralized. These results indicate that activation of Ag‐specific Th2 cells early in the course of the immune response to a protein antigen provides an immunological environment rich in IL‐4, thus leading to the inhibition of cell‐mediated immunity.