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*
Department of Gynecologic Oncology, M. D. Anderson Cancer Center, Houston, TX 77030; and
Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19140
A newly described subset of monocytes has been identified in
peritoneal exudate cells (PEC) from the malignant ascites from patients
with ovarian cancer. These cells were characterized by the production
of IL-10 and TGF-ß2, but not IL-12, IL-1
, or TNF-, and they
expressed CD14, CD16, and CD54, but not HLA-DR, CD80, CD86, CD11a,
CD11b, or CD25 cell surface Ags. Since this subset of monocytes could
affect the modulation of tumor immune responses in vivo, studies were
undertaken to determine their effect on the activation and
proliferation of autologous T cells from the peritoneal cavity of
patients with ovarian carcinoma. Expression of cytokine-specific
transcripts in T cells was determined by RT-PCR. Transcripts for the
following cytokines were detected in patient specimens that also
contained the IL-10-producing monocytes IL-2 (12 of 17 specimens),
GM-CSF (9 of 17 specimens), IFN-
(6 of 17 specimens), and TNF- (4
of 17 specimens). Cytokine production by T cells was determined by
intracellular flow cytometry and by ELISA. IL-2 and IFN- proteins,
unlike their transcripts, were detected only in specimens that lacked
IL-10-producing monocytes. IL-10-producing monocytes cocultured with
autologous T cells inhibited the proliferation of the T cells in
response to PHA. However, T cells cocultured with PEC from which the
IL-10-producing monocytes had been removed did not inhibit T cell
proliferation. Moreover, the inhibition of T cell proliferation by
IL-10-producing monocytes could be reversed by adding neutralizing Abs
to both IL-10R and TGF-ß2. These results suggest that this subset of
monocytes may modulate immune responses by inhibiting T cell
proliferation and cytokine protein production.
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