Bi-directional modulation of T cell-dependent antibody production by prostaglandin E(2).
T cell-dependent Ig production involves interaction between T cells and B cells. This study evaluated the effects of prostaglandin (PG) E(2) on Ig production in a system in which B cells were co-cultured with autologous CD4(+) T cell clones non-specifically activated by anti-CD3. The effects of PGE(2) on T cell-dependent Ig production differed substantially, depending on the T cells employed. We selected six T cell clones that were able to enhance Ig production (resistant T cell clones) and six T cell clones that inhibited Ig production in the presence of PGE(2) (sensitive T cell clones) for comparison. The resistant T cells produced high levels (>1000 pg/ml) of IL-2 and/or IL-4, and expressed high CD40L, OX40 and CD45RA, and low CD45RO. In contrast, sensitive T cells secreted low IL-2 (<500 pg/ml) and IL-4 (<200 pg/ml), and expressed low CD40, OX40 and CD45RA, and high CD45RO. Adding supernatant derived from resistant T cell clones restored Ig production inhibited by PGE(2), while removing IL-2, IL-4 or IL-10 using specific antibodies inhibited Ig production. In addition, we demonstrated a direct effect of PGE(2) on B cells to enhance Ig production. Consistently, in the presence of resistant T cells, PGE(2) increased B cell proliferation and differentiation. In conclusion, the effects of PGE(2) on Ig production consist of its indirect effects through T cells and its direct effects on B cells. The outcome of the effects can be up-regulatory or down-regulatory, depending whether resistant or sensitive T cells are involved.
He
Xiaowen
X
Research Service 151, VA Medical Center Memphis, 1030 Jefferson Avenue, TN 38104, USA.
Weyand
Cornelia M
CM
Goronzy
Jörg J
JJ
Zhong
Wanyun
W
Stuart
John M
JM
D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000096:biosynthesis; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D017252:CD3 Complex; D007136:Immunoglobulins; D007378:Interleukins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand; D015232:Dinoprostone