In vitro maturation of neonatal human CD8 T lymphocytes into IL-4- and IL-5-producing cells.
Naive CD8 T cells isolated from umbilical cord blood were examined for cytokine production and for surface phenotype before and after priming with anti-CD3 mAb in the presence of selected cytokines. On stimulation with anti-CD3 immobilized on CD32-B7-transfected L cells, naive and primed CD8 T cells release high levels of IFN-gamma but no IL-2, IL-4, or IL-5. IL-12-primed cells, and to a lesser extent IL-2-primed cells, have an increased capacity to produce IFN-gamma but display the same restricted pattern of cytokine production. Cells primed in the presence of IL-4 or IL-4 + IL-2 are capable of producing high levels of IL-5 but no IL-4, and their IFN-gamma-producing capacity is much reduced. Cells primed with both IL-4 + IL-12 produce high levels of IL-5 and IFN-gamma but no IL-4. IL-4-producing CD8 T cells are obtained only if IL-4- or IL-4 + IL-2-primed cells are subjected to a second cycle of activation in the presence of IL-2; restimulation of IL-4 + IL-12-primed cells under identical conditions fails to generate IL-4-producing cells but leads to the development of high IFN-gamma and IL-5 producers. Thus, unlike in CD4 T cells, IL-12 completely inhibits IL-4-induced capacity of CD8 T cells to produce IL-4. However, IL-4 and IL-12 synergize to promote the expression of IL-5. Regardless of the priming conditions, primed CD8 T cells are CD45ROhigh/RA-, CD31high and more than 50% are CD4+/CD8+; activated naive or primed CD8 T cells do not express CD40 ligand.
University of Montreal, Notre Dame Hospital Research Center, Canada.
D G
DG
Byun
C E
CE
Demeure
L P
LP
Yang
U
U
Shu
H
H
Ishihara
N
N
Vezzio
M K
MK
Gately
G
G
Delespesse
D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D011863:Radioimmunoassay
D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma