International Immunology, Vol. 14, No. 1, 69-77,
January 2002
© 2002 Japanese Society for Immunology
Bi-directional modulation of T cell-dependent antibody production by prostaglandin E2
1 Research Service 151, VA Medical Center Memphis, 1030 Jefferson Avenue, TN 38104, USA
2 Department of Medicine, University of Tennessee, Memphis, TN 38104, USA
3 Department of Medicine, Mayo Clinic and foundation, Rochester, MN 55905, USA
Correspondence to: X. He
T cell-dependent Ig production involves interaction between T cells and B cells. This study evaluated the effects of prostaglandin (PG) E2 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 PGE2 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 PGE2 (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 PGE2, while removing IL-2, IL-4 or IL-10 using specific antibodies inhibited Ig production. In addition, we demonstrated a direct effect of PGE2 on B cells to enhance Ig production. Consistently, in the presence of resistant T cells, PGE2 increased B cell proliferation and differentiation. In conclusion, the effects of PGE2 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.
Keywords: B lymphocytes, cytokines, Ig, inflammatory mediators, T lymphocytes
Transmitting editor: S. L. Swain
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