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*
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
Department of Microbiology and Immunology, University of Kentucky Medical Center, University of Kentucky, Lexington, KY 40536; and
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852
Patients with gliomas exhibit deficient in vitro and in vivo T cell
immune activity, and human glioblastoma culture supernatants (GCS)
inhibit in vitro T lymphocyte responses. Because APC are essential for
initiating and regulating T cell responses, we investigated whether GCS
would affect cytokines produced by monocytes and T cells from healthy
donors of PBMC. Incubation of PBMC with GCS decreased production of
IL-12, IFN-
, and TNF-
, and increased production of IL-6 and
IL-10. The GCS-induced changes in IL-12 and IL-10 occurred in
monocytes, and involved changes in IL-12 p40 and IL-10 mRNA expression.
Incubation with GCS also resulted in reduced expression of MHC class II
and of CD80/86 costimulatory molecules on monocytes. The
immunosuppressive effects were not the result of IL-6 or TGF-ß1 that
was detected in GCS. However, it was due to a factor(s) that is
resistant to pH extremes, differentially susceptible to temperature,
susceptible to trypsin, and has a minimum molecular mass of 40
kDa. Our findings show that glioblastoma-generated factors that are
known to suppress T cell responses alter the cytokine profiles of
monocytic APC that, in turn, inhibit T cell function. This model
indicates that monocytes can serve as an intermediate between
tumor-generated immune-suppressive factors and the T cell responses
that are suppressed in gliomas.
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