Default development of cloned human naive CD4 T cells into interleukin-4- and interleukin-5- producing effector cells.
It was recently demonstrated that naive human and mouse CD4 T cells release low but sufficient levels of interleukin (IL)-4 at priming to support their development into IL-4 producers. To determine whether this IL-4 is produced by a minor subset of cells, freshly isolated human naive CD4 T cells were directly cloned by limiting dilution in the absence of exogenous IL-4. More than 95% of neonatal and 60% of adult naive T cells seeded in single-cell cultures could be expanded upon stimulation with anti-CD3 mAb immobilized on CD32-B7.1 L cell transfectants in the presence of IL-2. All 171 clones derived from four neonates and two adults produced IL-4 and IL-5 at generally high levels. Like the allergen-specific human Th2 clones described in the literature, these T cell clones produced little or no interferon-gamma upon stimulation via their T cell receptor/CD3 complex, whereas they released high levels of this cytokine when activated with phorbol 12-myristate 13-acetate+ionomycin. Cells cloned and expanded in the presence of anti-IL4 + anti-IL-4R mAb produced much lower levels of IL-4 and IL-5. It is concluded that almost every single naive human CD4 T cell primed and expanded in the absence of exogenous IL-4 releases sufficient autocrine IL-4 to support its clonal expansion into high IL-4/IL-5 producers.
Yang
L P
LP
University of Montreal, Louis-Charles Simard Research Center, Notre-Dame Hospital, Montreal, Canada.
Byun
D G
DG
Demeure
C E
CE
Vezzio
N
N
Delespesse
G
G
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*
D015848:Interleukin-5; D015847:Interleukin-4