Human Th2-like cell clones induce IL-12 production by dendritic cells and may express several cytokine profiles.
Previous studies have shown that human Th2 cells, unlike their murine counterparts, retain the ability to produce IFN-gamma upon activation in the presence of exogenous IL-12. Here we first extended this notion by showing that Th2-like cell clones (Th2C) are also capable of inducing IL-12 production by physiological antigen-presenting cells (APC); we next showed that these cells may express several distinct cytokine profiles depending upon the activation signal and the type of APC with which they interact. We have analyzed the production of IL-4, IL-5 and IFN-gamma by Th2C stimulated by either anti-CD3 mAb or exogenous IL-2, using peripheral blood monocytes or dendritic cells (DC) as accessory cells. We found that: (I) DC but not monocytes released IL-12 and promoted IL-12-dependent IFN-gamma production upon interaction with anti-CD3- or IL-2-stimulated Th2C and (II) ligation of CD3 was required for the production of IL-4 but not of IL-5 or IFN-gamma. Thus, depending upon the type of APC with which they interacted and the mode of activation, Th2C, expressed four distinct cytokine profiles: (i) IL-4 + IL-5, in response to anti-CD3 + monocytes; (ii) IL-4, IL-5 + IFN-gamma, in response to anti-CD3 + DC; (iii) IL-5 + IFN-gamma, in response IL-2 + DC; and (iv) IL-5 alone, in response to IL-2 + monocytes. The ability of human Th2-like cells to induce IL-12 production and to release the proinflammatory cytokines IFN-gamma and IL-5 upon IL-2-driven interactions with APC may contribute to explain how local infection exacerbates Th2-mediated diseases, like bronchial asthma and atopic dermatitis.
Vezzio
N
N
Allergy Research Laboratory, Louis-Charles Simard Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.
Sarfati
M
M
Yang
L P
LP
Demeure
C E
CE
Delespesse
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis* / Q000145:classification*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D018664:Interleukin-12