Abstract
We have investigated alloantigen differences which stimulate lymphokine release and3H-TdR uptake in primary ‘one-way’ MLC among allogeneic mice. When mice differing at the wholeH-2 region were tested, MIF and immune IF release was observed, along with a marked3H-TdR uptake. Differences atK, D, orI-S-G regions stimulate both lymphokine release and3H-TdR uptake, though stronger immune IF and3H-TdR responses were observed with differences atI-S-G regions. On the other hand, when mice differing in their minor histocompatibility antigens, and notably at theMls locus, were tested, lymphokine release took place even in the absence of proliferation. Lastly, in MLC between mice differing at multiple minor loci, butH-2 andMls matched, MIF release only, and not immune IF and3H-TdR responses were observed in a few combinations. These findings show that T lymphocytes can recognize alloantigens by releasing lymphokines even without going through proliferation. Moreover, different levels of T-lymphocyte activation exist, depending on the kind of stimulating alloantigens present.
Similar content being viewed by others
References
Bach, F.: Genetic and cellular aspects of mixed leucocyte culture and cell-mediated lympholysis reactions.In D. H. Katz and B. Benacerraf (eds.):The Role of Products of the Histocompatibility Complex in Immune Response, pp. 103–129, Academic Press, New York, 1976
Bartfeld, H. and Atoynatan, T.: Activity and properties of macrophage migration inhibitory factor produced by mixed lymphocyte cultures.Nature New Biol. 230:246–249, 1971
Bloom, B. R. and Shevach, E.: Requirement for T cells in the production of migration inhibition factor.J. Exp. Med. 142:1306–1311, 1975
Campbell, J. B., Gruberger, T., Kochman, M. A., and White, S. L.: A microplaque reduction assay for human and mouse interferon.Can. J. Microbiol. 3:1247–1253, 1975
Cerottini, J. C. and Brunner, T. K.: Cell-mediated cytotoxicity, allograft rejection, and tumor immunity.Adv. Immunol. 18:67–132, 1974
Cochran, W. G. (ed.):Sampling Techniques. John Wiley and Sons, New York, 1977
David, J. R. and David, R. R.: Cellular hypersensitivity and immunity. Inhibition of macrophage migration and the lymphocyte mediators.Prog. Allergy 16:300–449, 1977
David, J. R. and Remold, H. G.: Macrophage activation by lymphocyte mediators and studies on the interaction on macrophage inhibitory factor (MIF) with its target cell.In D. S. Nelson (ed.):Immunobiology of the Macrophage, pp. 401–426, Academic Press, New York, 1976
Festenstein, H.: Pertinent features of M locus determinats including revised nomenclature and strain distribution.Transplantation 18: 555–564, 1974
Forni, G., Shevach, E. M., and Green, I.: Mutant lines of guinea pig L2C leukemia. I. Deletion of Ia alloantigens is associated with loss in immunogenicity of tumor-associated transplantation antigens.J. Exp. Med. 143:1067–1081, 1976
Forni, G., Giovarelli, M., Varesio, L., and Landolfo, S.: How are membrane antigens recognized by host immune system?In R. B. Herberman, S. Ferrone and R. A. Reisfield:Current Trends in Tumor Immunology, Garland Press, New York, in press 1979
Gifford, G. E., Tibor, A., and Peavy, D. L.: Interferon production in mixed lymphocyte cell cultures.Infect. Immun. 3:164–166, 1971
Gorski, A. J., Dupont, B., Nansen, J. A., and Good, E. A.: Leukocyte migration inhibitory factor (LMIF) production in unidirectional mixed lymphocyte cultures.J. Immunol. 117:865–870, 1976
Häyry, P. and Defendi, V.: Mixed lymphocyte cultures produce effector cells. An in vitro model for allograft rejection.Science 168:133–135, 1970
Herberman, R. B.: Cell-mediated immunity to tumor cells.Adv. Cancer Res. 19:206–264, 1974
Herberman, R. B. and Holden, H. T.: Natural cell-mediated immunity.Adv. Cancer Res. 27:305–357, 1978
Katz, D. H.:Lymphocyte Differentiation, Recognition and Regulation. Academic Press, New York, 1977
Kirchner, H., Zavatzky, R., Schirmacher, V.: Interferon production in the murine mixed lymphocyte culture. I. Interferon production caused by differences in the H-2K and H-2D region but not by differences in the I region or the M locus.Eur. J. Immunol. 9:97–99, 1979
Klein, J.: Biology of the Mouse Histocompatibility-2 Complex. Springer-Verlag, Berlin-Heidelberg-New York, 1975
Klein, J.: Genetics of cell-mediated lymphocytotoxicity in the mouse.In P. A. Miescher and H. J. Mueller-Eberhard (eds.):Springer Seminars in Immunopathology, pp. 31–49, Springer-Verlag, Berlin-Heidelberg-New York, 1978
Landolfo, S., Herberman, R. B., and Holden, H. T.: Cellular immunity to murine sarcoma virus inducedtumors as measured by macrophage migration inhibition assays.J. Natl. Cancer Inst. 6:1675–1683, 1977a
Landolfo, S., Herberman, R. B., and Holden, H. T.: Two mechanisms of migration inhibition factor induction by tumor antigens.Nature 270:62–64, 1977b
Landolfo, S., Herberman, R. B., and Holden, H. T.: Macrophage-lymphocyte interaction in migration inhibition factor (MIF) production against soluble or cellular tumor-associated antigens. I. Characteristics and genetic control of two different mechanisms of stimulating MIF production.J. Immunol. 121:695–701, 1978
Landolfo, S., Giovarelli, M., and Forni, G.: Alloantigen requirement for nonproliferative activation of T-lymphocytes.Transplantation 27:90–91, 1979
Lonai, P., McDevitt, H. O.: The expression of I region gene products on lymphocytes. II. Genetic localization and cellular distribution of MLR determinants.Immunogenetics 4:33–55, 1977
Lucas, D., and Klimpel, G.: Parameters of lymphocyte activation.In D. Lucas (ed.):Regulatory Mechanisms in Lymphocyte Activation, pp. 76–89, Academic Press, New York, 1977
Meo, T., Vives, G., Rijnbeek, A. M., Miggiano, V. C., Nabholz, M., and Shreffler, D. C.: A bipartite interpretation and tentative mapping of H-2 associated MLR determinants in the mouse.Transplant. Proc. 5:1339–1350, 1973
Newman, W., Gordon, S., Hammerling, U., Senik, A., and Bloom, B. R.: Production of migration inhibition factor (MIF) and an inducer of plasminogen activator (IPA) by subsets of T cells in MLC.J. Immunol. 120:927–932, 1978
North, R. J.: The concept of activated macrophages.J. Immunol. 121:806–809, 1978
Remold, H. G., and David, J. R.: Migration inhibition factor and other mediators in cell-mediated immunity.In R. T. McCluskey and S. Cohen (eds.):Mechanisms of Cell-Mediated Immunity, pp. 25–42, John Wiley and Sons, New York, 1974
Resch, K.: Membrane associated events in lymphocyte activation.In P. Cuatrecasas and M. F. Greaves (eds.):Receptors and Recognition, pp. 61–117, Chapman and Hall, London, 1976
Rocklin, R. E.: Production of migration inhibition factor by non-dividing lymphocytes.J. Immunol. 110:674–678, 1973
Svet-Moldavsky, G. J., Nemirovskaya, B. M., and Osipova, T. V.: Interferogenicity and antigen recognition.Nature 247:205–207, 1974
Thomas, D. W., Forni, G., Shevach, E. M., and Green, I.: The role of the macrophage as the stimulator cell in contact sensitivity.J. Immunol. 118:1677–1681. 1977
Trinchieri, G. and Santoli, D.: Anti-viral activity induced by culturing lymphocytes with tumor-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. 147:1314–1333, 1978
Virelizier, J. L., Allison, A. C., and de Mayer, E.: Production by mixed lymphocyte cultures of a Type II Interferon able to protect macrophages against virus infections.Infect. Immun. 17:282–285, 1977
Von Boehmer, H. and Sprent, J.: Expression of M locus differences by B cells but not T cells.Nature 249:383–365, 1974
Wagner, H., Rollingoff, M., and Nossal, G. J.: T-cell mediated immune response induced in vitro: a probe for allograft and tumor immunity.Transplant. Rev. 17:3–48, 1973
Wedner, J. N. and Parker, C. W.: Lymphocyte activation.Prog. Allergy 20:195–248, 1976
Youngner, J. S. and Salvin, S. B.: Production and properties of migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity.J. Immunol. 111:1914–1922, 1973
Youngner, J. S.: Properties of interferon induced by specific antigens.Tex. Rep. Biol. Med. 35:17–22, 1977
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Landolfo, S., Marcucci, F., Giovarelli, M. et al. Lymphokine production in mouse mixed lymphocyte reaction (MLR). Immunogenetics 9, 245–253 (1979). https://doi.org/10.1007/BF01570418
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01570418