Human memory T cell differentiation into Th2-like effector cells is dependent on IL-4 and CD28 stimulation and inhibited by TCR ligation.
Freshly isolated memory T cells primarily produced IL-2 and small amounts of IL-4 and IFN-gamma after stimulation in vitro. Priming for 5 days in vitro with anti-CD28 monoclonal antibodies (mAb) alone markedly increased production of IL-4. In comparison to fresh cells, the increase in the amount of IL-4 secreted reflected a marked increase in the number of IL-4-producing cells. Stimulation with immobilized anti-CD3 mAb during priming limited subsequent IL-4 production. By contrast, IFN-gamma production from in vitro primed memory T cells was directly correlated to the concentration of priming anti-CD3 mAb. IL-2 production by all restimulated cells was decreased. The differentiation of IL-4-producing cells could be blocked by antibody to IL-4 and enhanced by the addition of recombinant IL-4 as well as antibody to IFN-gamma. Of note, the IL-4-producing effector cells induced from in vitro priming derived from the early CD27pos memory T cell subset, whereas the small CD27neg differentiated memory subset produced IL-4 without in vitro priming. The results indicate that memory T cells can be directed to differentiate into IL-4-producing effector cells by stimulation via CD28 and IL-4, whereas increasing engagement of the TCR limits Th2 memory cell differentiation.
University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas 75235-8884, USA.
H
H
Schulze-Koops
P E
PE
Lipsky
L S
LS
Davis
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma