IL-4 from Th2-type cells suppresses induction of delayed-type hypersensitivity elicited shortly after immunization.
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-gamma 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 hyper-sensitivity 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-gamma 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.
Jacysyn
Jacqueline F
JF
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Abrahamsohn
Ises A
IA
Macedo
Mahasti S
MS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000628:therapy; D007114:Immunization; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation
D000911:Antibodies, Monoclonal; D016753:Interleukin-10; D015847:Interleukin-4; D010047:Ovalbumin