Summary
Lymphocytes isolated from axillary lymph nodes draining breast carcinoma were tested for natural killer (NK) activity against K562 in a 4-h 51Cr-release assay, and the in vitro effects of interferon (IFN) and OK432 (a streptococcal preparation) on their cytotoxicity were examined in comparison with NK activity of autologous peripheral blood lymphocytes (PBL). The levels of NK activity were lower in lymph node lymphocytes (LNL) than in PBL of the same patients. Significant levels of LNL-mediated lysis were recorded in 14 of 42 (33%) lymph node samples and in nine of 14 (64%) patients. Purification of large granular lymphocytes (LGL) from lymph node cells by discontinuous Percoll density gradient centrifugation resulted in an induction or enhancement of cytotoxic activity, with no reactivity in LGL-depleted, small T-lymphocyte populations. Positive reactions were observed with 10 of 13 (77%) LGL samples. The low reactivity of LNL was not attributable to coexistent suppressor cells for NK function, since lymph node cells failed to suppress NK activity of normal PBL. Partially purified human IFN and OK432 augmented NK activity of patients' PBL in approximately 70% and 90% of the cases, respectively, while LNL-mediated lysis was augmented in only 7% and 36% of the lymph node samples by IFN and OK432, respectively. These results indicate that K562-reactive NK cells and/or their precursors may frequently be present at subthreshold levels in the lymph nodes draining breast carcinoma, and that the augmentation of LNL-mediated cytotoxicity by OK432 might provide a local potentiation of natural immune function at the host-tumor interface rather than IFN.
Similar content being viewed by others
References
Antonelli P, Stewart W II, Dupont B (1981) Distribution of natural killer cell activity in peripheral blood, cord blood, thymus, lymph nodes and spleen and the effect of in vitro treatment with interferon preparation. Clin Immunol Immunopathol 19:161
Cudkowicz G, Hochman PS (1979a) Do natural killer cells engage in regulated reactions against self to ensure homeostasis? Immunol Rev 44:13
Cudkowicz G, Hochman PS (1979b) Regulation of natural killer activity by macrophage-like and other types of suppressor cells. In: Siskind GW, Litwin SD, Weksler ME (eds) Developemental immunology. Grune & Stratton, London, p 1
Cunningham-Rundles S (1982) Control of natural cytotoxicity in the regional lymph node in breast carcinoma. In: Herberman RB (ed) NK cells and other natural effector cells. Academic Press, New York, p 1133
Cunningham-Rundles S, Fillipa DA, Braun DW Jr, Antonelli P, Ashikari H (1981) Natural cytotoxicity of peripheral blood lymphocytes and regional lymph node cells in breast cancer in women. J Natl Cancer Inst 67:585
Droller MJ, Borg H, Perlman P (1979) In vitro enhancement of natural and antibody-dependent lymphocyte-mediated cytotoxicity against tumour targets by interferon. Cell Immunol 47:248
Einhorn S, Bolmgren H, Strander H (1978) Interferon and spontaneous cytotoxicity in man. I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon. Int J Cancer 22:405
Eremin O, Ashby J, Stephens JP (1978) Human natural cytotoxicity in the blood and lymphoid organs of healthy donors and patients with malignant disease. Int J Cancer 21:35
Herberman RB (1980) Natural cell-mediated immunity against tumors. Academic Press, New York
Herberman RB (1982) NK cells and other natural effector cells. Academic Press, New York
Hochman PS, Cudkowicz G (1979) Suppression of natural cytotoxicity by spleens of hydrocortisone-treated mice. J Immunol 123:968
Hochman PS, Cudkowicz G, Dausset J (1978) Decline of natural killer cell activity in sublethally irradiated mice. J Natl Cancer Inst 61:265
Kimber I, Moore M, Howell A, Wilkinson MJS (1983) Native and inducible levels of natural cytotoxicity in lymph nodes draining mammary carcinoma. Cancer Immunol Immunother 15:32
Mantovani A, Allavena P, Sessa C, Bolis G, Mangioni C (1980) Natural killer activity of lymphoid cells isolated from human ascitic ovarian tumors. Int J Cancer 25:573
Moore M, Potter MR (1980) Enhancement of human natural cell-mediated cytotoxicity by interferon. Br J Cancer 41:378
Moore M, Vose BM (1981) Extravascular natural cytotoxicity in man: Anti-K562 activity of lymph-node and tumor-infiltrating lymphocytes. Int J Cacer 27:265
Okamoto H, Shoin S, Koshimura S, Shimizu R (1967) Studies on the anticancer and streptolysin S-forming abilities of hemolytic streptococci. Jpn J Microbiol 11:323
Potter MR, Moore M (1978) Organ distribution of natural cytotoxicity in the rat. Clin Exp Immunol 34:78
Saksela E, Timonen T, Cantell K (1979a) Human natural killer cells is augmented by interferon via recruitment of “pre-NK” cells. Scand J Immunol 10:257
Saksela E, Timonen T, Ranki A, Häary P (1979b) Morphological and functional characterization of isolated effector cells responsible for human natural killer activity to fetal fibroblast and to cultured cell line targets. Immunol Rev 44:71
Savary CA, Lotozova E (1978) Suppression of natural killer cell activity by splenocytes from Corynebacterium parvum-injected, bone marrow-tolerant, and infant mice. J Immunol 120:239
Timonen T, Ortaldo JR, Herberman RB (1981) Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 153:569
Timonen T, Ortald JR, Herberman RB (1982) Analysis by a single cell cytotoxicity assay of natural killer (NK) cell frequencies among human large granular lymphocytes and of the effects of interferon on their activity. J Immunol 128:2514
Trichieri G, Santoli D (1978) Anti-viral activity induced by culturing lymphocytes with tumour-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med 147:1314
Uchida A, Micksche M (1981a) In vitro augmentation of natural killing activity by OK-432. Int J Immunopharmacol 3:365
Uchida A, Micksche M (1981b) Natural killer cells in carcinomatous pleural effusions. Cancer Immunol Immunother 11:131
Uchida A, Micksche M (1981c) Suppressor cells for natural killer activity in carcinomatous pleural effusions of cancer patients. Cancer Immunol Immunother 11:255
Uchida A, Micksche M (1982) Augmentation of human natural killing activity by OK-432. In: Herberman RB (ed) NK cells and other natural effector cells. Academic Press, New York, p 431
Uchida A, Micksche M (1983a) Intrapleural administration of OK432 in cancer patients: Activation of NK cells and reduction of suppressor cells. Int J Cancer 31:1
Uchida A, Micksche M (1983b) Lysis of fresh human tumor cells by autologous large granular lymphocytes from peripheral blood and pleural effusions. Int J Cancer 32:37
Uchida A, Yanagawa E, Micksche M (1983) In vivo and in vitro regulation of NK and auto-tumor killing activity by OK432. Proc 13th Int Congress Chemother
Vose BM, Vánky F, Argov S, Klein E (1977) Natural cytotoxicity in man: Activity of lymph node and tumour-infiltrating lymphocytes. Eur J Immunol 7:753
Yanagawa E, Uchida A, Kokoschka EM, Micksche M (1984) Natural cytotoxicity of lymphocytes and monocytes and its augmentation by OK432 in melanoma patients. Cancer Immunol Immunother 16:131
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yanagawa, E., Uchida, A. & Micksche, M. Natural cytotoxicity of lymphocytes from lymph nodes draining breast carcinoma and its augmentation by interferon and OK432. Cancer Immunol Immunother 17, 1–6 (1984). https://doi.org/10.1007/BF00205490
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205490