Selenium (Se) has been well documented as a modulator of natural killer (NK) cell function, however, the immunomodulatory mechanism(s) by which Se functions is not well understood. Previous in vitro studies on the effect of Se on NK cell function used mixed lymphocyte populations or enriched NK cell populations from peripheral blood or spleen. To alleviate extraneous variables, we assessed the effects of Se compounds on the cytotoxic activity of a human, non-transformed, NK cell line (NK3.3) derived from a mixed lymphocyte culture from normal donors. Phenotypically, the NK3.3 cell tine is CD2, CD3 , CD4-, CDS , CD16(FcYRIIIA), CD38, CD45, CD56 HLA-DR', -DP, DQ, Leu7, does not produce transcripts for the a, , or y chains of the TCR , and is 1L-2 dependent (J. Kornbluth, Univ. of Arkansas, Little Rock, AR). NK3.3 cells were treated overnight (18 hr) with 0 - 2.5 u.g Se/ml as sodium selenite (Na2SeO3) or selenomethionine (SeMet). Following Se treatment, NK3.3 cells were assessed for antibody-dependent-cell-cytotoxicity (ADCC) against Raji cells, natural cytotoxicity against K562 cells, granule release (serine esterase activity), and CD16 cell surface receptor expression. The data indicate Na2SeO3 decreases NK3.3 ADCC and natural cytotoxicity dose-dependently, whereas SeMet had no effect. Neither NK3.3 serine esterase activity nor CD 16 receptor expression on NK3.3 cells were affected by Na2SeOj or SeMet. These results suggest NajSeO, is a more effective modulator of NK3.3 cytotoxicity than SeMet and the mechanism(s) by which Se suppresses cytotoxicity is not related to granule release or CD16 receptor expression. Other steps in the signal transduction pathway are being investigated.
|State||Published - 1 Dec 1996|