Kazuo Komiyama

Inhibition of natural killer cell activity by IgA

The in vitro effect of IgA on natural killer (NK) activities of human peripheral blood mononuclear cells was investigated. Purified myeloma polymeric IgA2 (pIgA2) and secretory IgA (S-IgA) from human colostrum inhibited NK activity, while myeloma polymeric IgA1 (pIgA1), monomeric IgA1 (mIgA1), IgG, and IgM were ineffective. Inhibition was proportional to the concentration of pIgA2 (0.125-1 mg/ml) and was observed after as little as 1 hr of incubation at various effector to K562 target cell ratios. pIgA2 and S-IgA also inhibited NK activity of NK cell-enriched lymphoid cells and gamma-interferon-treated effector cells, but did not interfere with effector-target cell binding. The inhibitory effect was slightly diminished after 24 hr culture in pIgA2-free medium. Inhibition of cytotoxicity was not due to direct toxicity on lymphoid cells by IgA because PBL treated with pokeweed mitogen in the presence of pIgA2 or S-IgA differentiated into immunoglobulin-producing cells. Viability after 24 hr of preculture with pIgA2 and S-IgA was comparable to that of untreated control cells. Morphological examination of effector cells cultured with pIgA2 or S-IgA showed a decrease in the number of granules, and the formation of cytoplasmic vacuoles. These morphological changes appeared to coincide with the depressed cytotoxicity of NK cells. The results demonstrate that purified pIgA2 and S-IgA have significant immunomodulatory effects on human NK activity.

Natural killer cells in human colostrum

The presence of natural killer cells in human colostrum was disclosed with the use of a fluorochrome-labeled monoclonal antibody HNK-1 (Leu-7) that recognizes cells with natural killer and killer activity. Approximately 0.5% of total colostral cells were stained with this reagent. These cells were separated by the fluorescence-activated cell sorter and examined for their morphology by electron microscopy and for their cytotoxic activity against 51Cr-labeled K562 target cells. Two morphological types of natural killer cells were observed in colostrum: the first was represented by large cells with numerous vacuoles but without dense cytoplasmic granules; the second type, which occurred with lower frequency, resembled the large granular lymphocytes associated with natural killer activity in peripheral blood. The HNK-1-positive cells from colostrum displayed low cytotoxic activity against K562 target cells. Incubation of HNK-1-positive cells from peripheral blood with cell-free colostrum resulted in a dose-dependent inhibition of the cytotoxic activity. The functional changes were accompanied by morphological alterations which included degranulation and the formation of numerous vacuoles. The variances in the cytotoxic activity of peripheral blood HNK-1-positive cells suspended in different dilutions of colostrum suggest that this fluid contains humoral factors which modify morphology and function depending on their concentrations.

Malignant lymphoma arising from postoperative benign lymphoepithelial lesion. Report of a case and review of literature.

患者は42歳女性。約3年前から両側耳下腺部が腫張し, その増大と口腔乾燥感の増強のため1993年7月当科を受診した。顔貌はび漫性に両側耳下腺部が腫脹し, 触診で, 左側では比較的境界明瞭な鶏卵大の弾力性やや硬の腫瘤1個, 右側では胡桃大の同様の腫瘤2個を触知した。各種臨床検査および画像所見でも腫瘤に対する診断を確定しえず, 耳下腺腫瘍の可能性も考慮して確定診断を得る目的で左側耳下腺浅葉切除術を施行した。2か月後右側耳下腺浅葉切除術を施行した。病理組織学的診断はいずれもBenign lymphoepithelial lesion (LEL) であった。術後約1年を経過し, 左側の耳下腺部に大豆大の腫瘤が出現し漸次増大傾向を示したため, 1995年2月生検を行いdiffuse medium sized cell lymphomaと診断された。その後駿河台日大病院内科へ転科し, CHOP療法を5クール, MEK-2療法4クールの化学療法を受け1997年まで経過観察中である。本症例は, Pan B cellマーカーであるCD20陽性で, TcellマーカーであるCD3は陰性を示したところから, 耳下腺のリンパ上皮性疾患を基盤として発生したMALT lymphomaと診断した。

Inhibition of Natural Killer (NK) Activity by Human Colostral and Serum IgA

Natural killer (NK) cells are defined as effector cells with spontaneous cytotoxicity against tumor, virus-infected and undifferentiated normal cells. NK activity is closely associated with a subpopulation of lymphocytes, large granular lymphocytes (LGL), that contain azurophilic cytoplasmic granules. The NK cells show a characteristic organ distribution: they are numerous in peripheral blood and spleen, but relatively low numbers are found in lymph nodes, peritoneal cavity and bone marrow (1,2). Previous investigations have demonstrated that NK activity is influenced by various factors such as interferon, interleukin-2, hormones, suppressor cells, environmental factors and age. Recently, mucosal LGL have been isolated from the small intestines of humans, mice and rats (3–6). In the mouse and rat, mucosal LGL showed moderate levels of NK activity, while human mucosal LGL demonstrated low NK activity.