CD45 isoform expression is associated with different susceptibilities of human naive and effector CD4+ T cells to respond to IL-4.
Interleukin-4 (IL-4) is the major factor promoting the development of T helper type 2 (Th2) cells from naive precursor T cells. Minute amounts of IL-4 produced by naive T cells seem to be sufficient; however, the molecular mechanisms explaining this efficient utilization of IL-4 are not yet known. Here, we show that human CD4+ CD45RA+ naive T cells, in contrast to CD4+ CD45R0+ effector T cells, show responsiveness to endogenous as well as exogenous IL-4 to proliferate and differentiate towards Th2 cells in vitro. Despite production levels of IL-4 below conventional detection limits, CD45RA+ T cell-derived IL-4 could clearly activate STAT6. Although the expression levels of IL-4R and STAT6 were not different between naive and effector T cells, only naive T cells responded to IL-4 in a STAT6-dependent reporter gene assay. Transfecting a trans-dominant negative form of STAT6 abrogated IL-4-induced proliferation in CD45RA+ cells. A significantly higher protein tyrosine phosphatase (PTPase) activity was detected in CD45R0+ T cells as compared to CD45RA+ T cells. Cross-linking CD45 potently reduced PTPase activity in CD45R0+ T cells and restored their ability to proliferate in response to IL-4. Thus, CD45 PTPase activity contributes to the susceptibility of naive and memory T cells to respond to IL-4.
Stütz
Adrian
A
Novartis Institutes for Biological Research, Vienna, Austria.
Graf
Philipp
P
Beinhauer
Brigitte
B
Hammerschmid
Franz
F
Neumann
Christine
C
Woisetschläger
Maximilian
M
Jung
Thomas
T
D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D015704:CD4 Antigens; D020033:Protein Isoforms; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D017493:Leukocyte Common Antigens