A strict requirement of interleukin-4 for interleukin-4 induction in antigen-stimulated human memory T cells.
The role of interleukin-4 (IL-4) in the induction of IL-4 in mouse T cells is well established, but conflicting results have been reported with anti-CD3-primed human T cells and T cell clones. Therefore, IL-4 regulation was investigated in short-term cultured human T cells primed in vitro with either a superantigen or a hapten, nickel sulfate (NiSO4), for 3 days and expanded with IL-2 for another 5 days. Under these conditions, antigen-specific IL-4 producing T cells were generated in 35/40 cultures. Priming for IL-4 production was abrogated in all cultures by anti-IL-4 antibody or soluble IL-4 receptor (sIL-4R). Primed T cells that were IL-4- when cultured with IL-2 only developed an IL-4 producing phenotype when primed and expanded in the presence of exogenous IL-4. T cells primed in the presence of either endogenous or exogenous IL-4 produced 10-200-fold more IL-4 than T cells primed in the presence of anti-IL-4 antibody or sIL-4R. While IL-4 induction was absolutely dependent on IL-4, neither endogenous nor exogenous IL-4 influenced IFN-gamma synthesis. Most importantly, IL-4 induced and sIL-4R abolished priming for IL-4 production even in NiSO4-specific memory T cells from sensitized individuals. Thus, IL-4 induction in antigen-specific human memory T cell populations absolutely required IL-4. The IL-4 pathway of memory T cells retained a remarkable plasticity in sensitized individuals.
Breit
S
S
Department of Dermatology, Ludwig-Maximilians-University Munich, Germany.
Steinhoff
M
M
Blaser
K
K
Heusser
C H
CH
Sebald
W
W
Levine
A D
AD
Röcken
M
M
D000328:Adult; D000368:Aged; D000939:Epitopes / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D009532:Nickel / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*
D000939:Epitopes; D006241:Haptens; D015847:Interleukin-4; C029938:nickel sulfate; D009532:Nickel