Summary
Intralesional injection of BCG into an established line-10 hepatocellular carcinoma in the strain-2 guinea pig causes regression of the tumor and induction of line-10 immunity. We found that the animals were already protected for a second challenge with line-10 tumor cells 7 days after BCG treatment. We studied whether this early induction of immunity was correlated with the expression of MHC class II antigens on line-10 tumor cells and was correlated with an increased expression of MHC class II antigens on leukocytes in the primary tumor and in the regional lymph node (Ln. axillaris accessorius). The MHC class II antigens and the leukocyte subpopulations were measured with monoclonal antibodies and flow cytofluorometry. In the draining lymph node the number of nucleated cells increased about 10-fold during the first 5 days after intralesional injection of BCG. At this time the MHC class II antigen expression of these cells was increased from 21%–32% in the naive controls to 39%–53% in animals with BCG-treated tumors. This implies that the number of MHC-class-II-positive cells increased about 20-fold in the draining lymph node. Surprisingly, the increase in percentage of MHC-class-II-antigen-positive cells was mainly due to an increase of IgM-positive B cells from 8%–11% to 22%–41% and an increase of IgG-positive B cells from 7%–27% to 25%–44%. In the tumor, BCG treatment induced a small increase of MHC-class-II-antigen-positive cells from 11%–12% to 15%–20%. Probably this increase came not from tumor cells but mainly from a BCG-induced infiltration of mononuclear cells, as an increase of T cells from 14% to 20%, an increase of macrophages from 8% to 18%, and an increase of B cells from 0 to 6% was observed. We conclude that the potentiation of anti-(line-10 tumor cell) immunity correlated with a 20-fold increase of MHC-class-II-antigen-positive cells in the lymph nodes and a small increase in the number of MHC-class-II-antigen-positive tumor-infiltrating cells.
Similar content being viewed by others
References
Baldini L, Cortelezzi A, Polli N, Neri A, Nobili L, Maiolo AT, Lambertenghi-Deliliers G, Polli EE (1986) Human recombinant interferon α-2C enhances the expression of class II HLA antigens on hairy cells. Blood, 67: 458
Beller DI, Kiely JM, Unanue ER (1980) Regulation of macrophage populations. I Preferential induction of Ia-rich peritoneal exudate by immunological stimuli. Immunology 124: 1426
Benacerraf B (1985) Significance and biological function of class II MHC molecules. Am J Pathol 120: 334
Bernard DJ, Maurizis JC, Chassagne J, Chollet Ph, Plagne R (1985) Comparison of class II HLA antigen expression in normal and carcinomatous human breast cells. Cancer Res 45: 1152
Brown MF, Cook RG, Van Rich RR (1984) Cloned human T cells synthesise Ia molecules and can function as antigen presenting cells. Hum Immunol 11: 219
Burger R, Shevach EM (1980) Monoclonal antibodies to guinea pig Ia antigens. II Effect on alloantigen-, antigen-, and mitogen-induced T lymphocyte proliferation in vitro. J Exp Med 152: 1011
Burger R, Clement L, Schroer J, Chiba J, Shevach EM (1981) Monoclonal antibodies to guinea pig Ia antigens: I. Production, serologic and immunochemical characterization. J Immunol 126: 32
Burger R, Scher I, Sharrow SO, Shevach EM (1984) Non-activated guinea pig T cells and thymocytes express Ia antigens: FACS analysis with alloantibodies and monoclonal antibodies. Immunology 51: 93
Chesnut RW, Grey HM (1985) Antigen presenting cells and mechanisms of antigen presentation. Crit Rev Immunol 5: 263
De Jong WH, Steerenberg PA, Van de Plas MMT, Kruizinga W, Ruitenberg EJ (1985) T cell involvement in adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs. J Natl Cancer Inst 75: 483
Diedrichs M., Schendel D. J. (1989) Differential surface expression of class II isotypes on activated CD4 and CD8 cells correlates with levels of locus-specific mRNA. J Immunol 142: 3275
Evans R, Blake SS, Saffer, JD (1986) Expression of class II-MHC antigens by tumor-associated and peritoneal macrophages: systemic induction during tumor growth and tumor rejection. J Leukocyte Biol 40: 499
Forbes JT, Nakao Y, Smith RT (1975) Tumor-specific immunity to chemically induced tumors. Evidence for immunological specificity and shared antigenicity in lymphocyte responses to soluble tumor antigens. J Exp Med 141: 1181
Forni G, Shevach EM, Green I (1976) Mutant lines of guinea pig L2C leukemia: I. Deletion of Ia alloantigens is associated with a loss in immunogenicity of tumor associated transplantation antigens. J Exp Med 144: 1067
Garner RE, Malick AP, Elgert KD (1986) Variation in macrophage antigen phenotype: a correlation between Ia antigen reduction and immune dysfunction during tumor growth. J Leukocyte Biol 40: 561
Greiner JW, Hand PH, Noguchi PH, Fisher PB, Pestka S, Schlom J (1984) Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant human leukocyte α-interferon treatment. Cancer Res 44: 3208
Handwerger BS, Schwartz RS (1974) Separation of murine lymphoid cells using nylonwool columns. Transplantation 18: 544
Hanna MG Jr, Peters LC (1975) Efficacy of intralesional BCG therapy in guinea pigs with disseminated tumor. Cancer 36: 1298
Hanna MG Jr, Snodgrass MJ, Zbar B, Rapp HJ (1973) Histopathology of tumor regression after intralesional injection ofMycobacterium bovis: IV. Development of immunity to tumor cells and BCG. J Natl Cancer Inst 51: 1897
Healey DG, Agha N, Turk JL (1988) Behaviour of guinea pig T cells stimulated by antigen, allo-antigen, and mitogen. Int Arch Allergy Appl Immunol 87: 134
Hewitt CRA, Feldman M (1989) Human T cell clones present antigen. J Immunol 143: 762
Houghton AN, Eisinger M, Albino AP, Cairncross JG, Old LJ (1982) Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets. J Exp Med 156: 1755
Houghton AN, Thomson TM, Gross D, Oettgen HF, Old LJ (1984) Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human γ-interferon. J Exp Med 160: 255
Johnson SC, Zwilling BS (1985) Continuous expression of Ia antigen by peritoneal macrophages from mice resistant toMycobacterium bovis (strain BCG). J Leukocyte Biol 38: 635
Kaye PM, Feldmann M (1986) Regulation of macrophage accessory cell activity by mycobacteria: I. Ia expression in normal and irradiated mice infected withMycobacterium microti. Clin Exp Immunol 64: 20
Marrack P, Enders R, Shimonkevic R, Zlolnik A, Dialynas D, Fitch FW, Kappler J (1983) The major histocompatibilitiy complex-restricted antigen receptor on T cells: II. Role of the L3T4 product. J Exp Med 159: 1213
Mauer-Gross U, Von Steldern D, Hadding U, Bitter-Suermann D, Burger R (1985) Cell surface antigens on the guinea pig macrophage: identification by monoclonal antibodies and association with the activation state. Immunology 55: 519
Mshana RN, Hastings RC, Krahenbuhl JL (1988) Infection with live mycobacteria inhibits in vitro detection of Ia antigen on macrophages Immunobiology 177: 40
Poels LG, Jap PHK, Niekerk CV, Wellemen A, Chand A, Staal HJ, De Jong WH, Steerenberg PA (1984) Common and specific antigens on two tumor cell lines. Protides Biol Fluids Proc Collog. 31: 579
Powell PC, Hála K, Wick G (1987) Aberrant expression of Ia-like antigens on tumor cells of regressing but not of progressing Rous sarcomas. Eur J Immunol 17: 723
Prescott S, James K, Hargreave TB, Chisholm GD, Smyth JF (1989) Immunopathological effects of intravesical BCG treatment. Prog Clin Biol Res 310: 93
Rock KL, Benacerraf B (1983) MHC-restricted T cell activation: analysis with T cell hybridomas. Immunol Rev 76: 29
Shevach EM (1978) The guinea pig I-region. A functional analysis of Ia-Ir associations. Springer Semin Immunopathol 1: 207
Shevach EM, Rosenstreich DL, Green I (1973) The distribution of histocompatibility antigens on T and B cells in the guinea pig. Transplantation 16: 126
Shu S, Steerenberg PA, Hunter JT, Evans ChH, Rapp HJ (1981) Adoptive immunity to the guinea pig line 10 hepatoma and the nature of in vitro lymphoid-tumor cell interactions. Cancer Res 41: 3499
Shu S, Fonseca LS, Hunter JT, Rapp HJ (1983) Mechanisms of immunological eradication of a syngeneic guinea pig tumor: II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity. Transplantation 35: 56
Shu S, Fonseca LS, Kato H, Zbar B (1983) Mechanisms of immunological eradication of a syngeneic guinea pig tumor: participation of a component(s) of recipient origin in the expression of systemic adoptive immunity Cancer Res 43: 2637
Snodgrass MG, Hanna MG Jr (1973) Ultrastructural studies of histiocytetumor cell interactions during tumor regression after intralesional injection ofMycobacterium bovis. Cancer Res 33: 701
Steerenberg PA, De Jong WH, Elgersma A, Burger R, Poels LG, Claessen AME, Den Otter W, Ruitenberg EJ (1990) Tumor infiltrating leukocytes during progressive tumor growth and BCG mediated tumor regression Virchows Arch [B] (in press)
Tan BTG, Ekelaar F, Luirink J, Rimmelzwaan G, De Jonge AJR, Scheper RJ (1985) Production of monoclonal antibodies defining guinea pig T-cell surface markers and a strain 13 Ia-like antigen: the value of immunohistological screening. Hybridoma 4: 115
Unanue ER, Beller DI, Lu ChY, Allen PM (1984) Antigen presentation: Comments on its regulation and mechanism. J Immunol 132: 1
Van de Molengraft F, Poels LG, Van Niekerk CC, Mungyer G, Steerenberg PA, Jap PHK (1989) Changing tumor antigen expression in metastatic hepatocellular carcinoma cells of the guinea pig. Virchows Arch [B] 56: 211
Van Loveren H, De Weger R, Garssen J, Los G, Askenase PhW (1989) Impairment of allograft tumor immunity by isotype-like suppression of antigen-specific T cell factors. Transplantation 47: 504
Vespa L, Johnson SC, Aldrich WA, Zwilling BS (1987) Modulation of macrophage Ia expression: lack of effect of prostaglandins and glucocorticoids on macrophages that continuously express Ia. J Leukocyte Biol 41: 47
Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol 55: 283
Zbar B, Bernstein ID, Rapp HJ (1971) Suppression of tumor growth at the site of infection with living bacillus Calmette-Guérin. J Natl Cancer Inst 46: 831
Zbar B, Ribi E, Kelly M, Granger D, Evans C, Rapp HJ (1976) Immunological approaches to the treatment of human cancer based on a guinea pig model. Cancer Immunol Immunother 1: 127
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Steerenberg, P.A., De Jong, W.H., Geerse, E. et al. Major histocompatibility complex class II antigen expression during potentiation of line-10 tumor immunity after intralesional administration of bacillus Calmette-Guérin. Cancer Immunol Immunother 32, 95–104 (1990). https://doi.org/10.1007/BF01754205
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01754205