In vitro maturation of human neonatal CD4 T lymphocytes. II. Cytokines present at priming modulate the development of lymphokine production.
The development of naive CD4 T cells into type 1 or type 2 Th cells has been extensively analyzed in the mouse. Using neonatal CD4 T lymphocytes as a source of human naive cells, we report that these cells may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines. After 3 days of stimulation with anti-CD3 mAb immobilized on CD32 transfected mouse fibroblasts, followed by 3 days of culture in the presence of IL-2, neonatal cells acquire the phenotypic and functional characteristics of effector cells. Primed cells are enriched in CD45R0hi and CD31- cells, and upon stimulation with PMA+ ionomycin they release significant amounts of IL-2, IFN-gamma, IL-4, IL-5, and IL-10. Addition of exogenous cytokines during the period of activation with anti-CD3 markedly alters the profile of cytokine production by primed cells: 1) IL-2 uniformly enhances Th1 and Th2 cytokine production; 2) IL-4 markedly enhances the release of IL-4, IL-5, and IL-10 and suppresses that of IFN-gamma; 3) IFN-gamma strongly inhibits IL-4 and IL-5 production but slightly enhances IFN-gamma release; 4) IFN-alpha markedly inhibits IL-4 and IL-5 production and increases the production of both IFN-gamma and of IL-10; 5) TGF-beta suppresses IL-4 and IL-5 (and to a lesser extent IL-2) production but has inconsistent effect on IL-10 and IFN-gamma production. These effects of exogenous cytokines are not associated with an alteration of CD31 expression on primed cells.
Demeure
C E
CE
University of Montreal, Notre-Dame Hospital Research Center, Canada.
Wu
C Y
CY
Shu
U
U
Schneider
P V
PV
Heusser
C
C
Yssel
H
H
Delespesse
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D051379:Mice
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines