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Functional heterogeneity of human antigen-presenting cells: Presentation of soluble antigen but not self-Ia by monocytes

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These studies were undertaken to examine the phenotype of the antigen-presenting cells (APC) circulating in human peripheral blood. Cells adherent to glass were found to be efficient APC, restoring antigen-induced3H-thymidine incorporation to T4-positive T cells that had been rigorously depleted of contaminating APC. In order to identify the APC within the glass-adherent cells (AC), these cells were stained with a number of monocyte-specific monoclonal antibodies (Mo-Mab) including 3C10, 63D3, and 61D3, and the Mo-Mab-positive and -negative cells were separated with the fluorescence-activated cell sorter. This method of preparation yielded Mo-Mab(+) AC populations that were more than 98% positive for the relevant Mab when reanalyzed with the fluorescence-activated cell sorter. Less than 1% of the Mo-Mab(−) AC populations were positive when reanalyzed with the Mab used for the separation. However, each Mo-Mab(−) AC population was contaminated with variable numbers (4–60%) of Mo as detected by morphologic criteria, histochemical analysis for esterase activity, or staining with a different Mo-Mab. Both Mo-Mab(+) and (−) AC populations were found to be similarly effective APC, with as few as 500 cells/well supporting responses to streptokinase-streptodornase, tetanus toxoid, andCandida albicans antigen. In the absence of antigen, only 3C10(−), 63D3(−), or 61D3(−) AC consistently stimulated3H-thymidine incorporation of autologous T4 cells; large numbers (>5×103/well) of APC were necessary to induce this response. These results support the conclusion that cells identified by Mo-specific Mab are capable of functioning as APC, inducing3H-thymidine incorporation in response to exogenous antigens. However, Mo-Mab(+) AC are not unique in this activity since Mo-Mab(−) AC also appeared to be able to present antigen. These Mo-Mab(−) AC appear to contain the majority of cells inducing autologous T4-cell reactivity.

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  1. 1.

    Rosenthal AS, Shevach EM: Function of macrophages in antigen recognition by guinea pig T lymphocytes. J Exp Med 138:1194–1229, 1973

  2. 2.

    Ellner J, Lipsky PE, Rosenthal AS: Antigen handling by guinea pig macrophages: Further evidence for the sequestration of antigen relevant for activation of primed T lymphocytes. J Immunol 118:2053–2057, 1977

  3. 3.

    Ziegler K, Unanue ER: Identification of a macrophage antigen-processing event required for I-region restriction antigen presentation to T lymphocytes. J Immunol 127:1869–1875, 1981

  4. 4.

    Weinberger O, Herrmann S, Mescher MF, Benacerraf B, Burakoff SJ: Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: Evidence for antigen processing. Proc Natl Acad Sci 78:1796–1799, 1981

  5. 5.

    Scala G, Oppenheim JJ: Antigen presentation by human monocytes: Evidence for stimulant processing and requirement for interleukin 1. J Immunol 131:1160–1166, 1983

  6. 6.

    Allen PM, Beller DI, Braun J, Unanue ER: The handling ofListeria monocytogenes by macrophages: The search for an immunogenic molecule in antigen presentation. J Immunol 132:323–331, 1984

  7. 7.

    Sørdestrup HG, Rubin B, Sørensen SF, Svejgaard A: Importance of HLA-D antigens for the cooperation between human monocytes and T lymphocytes. Eur J Immunol 8:520, 1978

  8. 8.

    Todd RF, Reinherz EL, Schlossman SF: Human macrophage-lymphocyte interaction in proliferation to soluble antigen. I. Specific deletion of lymphocyte proliferative activity on macrophage monolayers. Cell Immunol 55:114–123, 1980

  9. 9.

    Geha RS, Jonsen ME, Ault BH, Yunis E, Broff MD: Macrophage T cell interaction in man: binding of antigen-specific human proliferating and helper T cells to antigen-pulsed macrophages. J Immunol 126:781–786, 1981

  10. 10.

    Barak V, Kuks Z, Galilli N, Treves AJ: Selection and continuous growth of antigen-specific human T cells by antigen-treated monocytes. Eur J Immunol 13:952–956, 1983

  11. 11.

    Möller G: Role of the macrophages in the immune response. Immunol Rev 40:1, 1978

  12. 12.

    Grey HM, Colon SM, Chesnut RW: Requirements for the processing of antigen by antigen presenting B cells. II. Biochemical comparison of the fate of the antigen in B cell tumors and macrophages. J Immunol 129:2389–2395, 1982

  13. 13.

    Chesnut RW, Colon SM, Grey HM: Antigen presentation by normal B cells, B cell tumors, and macrophages: Functional and biochemical comparison. J Immunol 128:1764–1768, 1982

  14. 14.

    Glimcher LH, Kim KJ, Green I, Paul WE: Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex restricted fashion to antigen-reactive T cells. J Exp Med 155:445–449, 1982

  15. 15.

    Issekutz T, Chu E, Geha RS: Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus lymphoblastoid cells. J Immunol 129:1446–1450, 1982

  16. 16.

    Berle EJ, Braathen LR, Thorsby E: HLA-D/DR restriction of Langerhans cell-dependent antigen activation by T lymphocytes. The same D/DR determinants are restriction elements on monocytes and Langerhans cells. Scand J Immunol 16:549–552, 1982

  17. 17.

    Van Voorhis WC, Hair LS, Steinman RM, Kaplan G: Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med 155:1172–1187, 1982

  18. 18.

    Van Voorhis WC, Valinsky J, Hoffman E, Luban J, Hair LS, Steinman RM: Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication. J Exp Med 158:174–191, 1983

  19. 19.

    Inaba K, Steinman RM, Van Voorhis EC, Muramatso S: Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci 80:6041–6045, 1983

  20. 20.

    Ashwell JD, DeFranco AL, Paul WE, Schwartz RE: Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation. J Exp Med 159:881–905, 1984

  21. 21.

    Fontana W, Fierz W, Wekerle H: Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature 307:273–276, 1983

  22. 22.

    Hirschberg A, Hirschberg T, Jaffe E, Thorsby E: Antigen presenting properties of human vascular endothelial cells: Inhibition by anti-HLA-DR antisera. Scand J Immunol 14:545–553, 1981

  23. 23.

    Rosenberg SA, Ligler FS, Ugolini V, Lipsky PE: A monoclonal antibody that identifies peripheral blood monocytes recognizes the accessory cells required for mitogen-induced T lymphocyte proliferation. J Immunol 126:1473–1477, 1981

  24. 24.

    Van Voorhis WC, Steinman RM, Hair LS, Luban J, Witmer MD, Koide S, Cohn ZA: Specific antimononuclear phagocyte monoclonal antibodies. Application to the purification of dendritic cells and the tissue localization of macrophages. J Exp Med 158:126–145, 1983

  25. 25.

    Nunez G, Ugolini V, Capra JD, Stastny P: Monoclonal antibodies against human monocytes. II. Recognition of two distinct cell surface molecules. Scand J Immunol 16:515–523, 1982

  26. 26.

    Boyum A: Isolation of mononuclear cells and granulocytes from human blood: Isolation of mononuclear cells by one centrifugation and of sedimentation at 1g. Scand J Clin Lab Invest 21 (Suppl 97):77, 1968

  27. 27.

    Kung PC, Goldstein G, Reinherz EL, Schlossman SF: Monoclonal antibodies defining distinctive cell surface antigens. Science 206:347–349, 1979

  28. 28.

    Lampson LA, Levy R: Two populations of Ia-like molecules on a human B cell line. J Immunol 125:293–299, 1980

  29. 29.

    Brodsky FM, Parham P, Bodmer WF: Monoclonal antibodies against HLA-DRw determinants. Tissue Antigens 16:30–48, 1980

  30. 30.

    Edidin M, Church JA: A quantitative fluorochromatic assay for alloantibodies. Transplantation 6:1010, 1968

  31. 31.

    Edidin M: A rapid, quantitative fluorescence assay for cell damage by cytotoxic antibodies. J Immunol 104:1303–1306, 1970

  32. 32.

    Koski IR, Poplack DG, Blaese RM: A nonspecific esterase stain for the identification of monocytes and macrophages.In In Vitro Methods of Cell-Mediated and Tumor Immunity. New York, Academic Press, 1976, pp 359–362

  33. 33.

    Thiele DL, Kurosaka M, Lipsky PE: Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: Delineation by its sensitivity to the lysosomotropic agent L-leucine methyl ester. J Immunol 131:2282–2290, 1983

  34. 34.

    Rosenberg SA, Lipsky PE: Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol 122:926–931, 1979

  35. 35.

    Wysocki LJ, Sato VL: “Panning” for lymphocytes: A method for cell selection. Proc Natl Acad Sci USA 75:2844, 1978

  36. 36.

    Herzenberg LA, Herzenberg LA: Analysis and Separation Using the Fluorescence Activated Cell Sorter (FACS). Oxford, Blackwell Scientific, 1978, pp 22.1–22.21

  37. 37.

    Thiele DL, Lipsky PE: The accessory function of phagocytic cells in human T cell and B cell responses. J Immunol 129:1033–1040, 1982

  38. 38.

    Crissman HA, Van Egmond J, Holdrinet RS, Pennings A, Haanen C: Simplified method for DNA and protein staining of human hematopoietic cell samples. Cytometry 2:59, 1983

  39. 39.

    MacDermot RP, Stacey MC: Further characterization of the human autologous mixed leukocyte reaction (MLR). J Immunol 126:729–734, 1981

  40. 40.

    Opelz G, Kiuchi M, Takasugi M, Terasaki PE: Autologous stimulation of human lymphocyte subpopulations. J Exp Med 142:1327–1333, 1975

  41. 41.

    Kuntz M, Innes JB, Weksler ME: Lymphocyte transformation induced by autologous cells. IV. Human T lymphocyte proliferation induced by autologous or allogenic non-T lymphocytes. J Exp Med 143:1042–1054, 1976

  42. 42.

    Nussenzweig MD, Steinmann RM: Contribution of dendritic cells to the murine syngeneic mixed leukocyte reaction. J Exp Med 151:1196–1212, 1980

  43. 43.

    Mingari MC, Moretta L: The role of la antigens in the human autologous mixed lymphocyte reaction. Eur J Immunol 12:98–100, 1982

  44. 44.

    Swierkosz JE, Rock K, Marrack P, Kappler JW: The role of H-2-linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper cells each specific for antigen and one set of parental H-2 products. J Exp Med 147:554–570, 1978

  45. 45.

    Reinherz EL, Kung PC, Goldstein G, Levy RH, Schlossman SF: Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci 76:4061, 1979

  46. 46.

    Reinherz EL, Kung PC, Goldstein G, Levy RH, Schlossman SF: A monoclonal antibody reactive with the human cytotoxic/suppressor T cell previously defined by a heteroanti-serum termed TH2. J Immunol 124:1301–1307, 1980

  47. 47.

    Shen HH, Talle MA, Goldstein G, Chess L: Functional subsets of human monocytes defined by monoclonal antibodies: A distinct subset of monocytes contains the cells capable of inducing the autologous mixed lymphocyte culture. J Immunol 130:698–705, 1983

  48. 48.

    Todd RF, Leeman EL, Daley JF, Schlossmann SF: Mo2: Functional properties of antigen-bearing cells. Clin Immunol Immunopathol 26:118–125, 1983

  49. 49.

    Morimoto C, Todd RF, Distaso JA, Schlossman SF: The role of the macrophage inin vitro primary anti-DNP antibody production in man. J Immunol 127:1137–1141, 1981

  50. 50.

    Gonwa TA, Picker LF, Raff HV, Goyert SM, Silver J, Stobo JB: Antigen-presenting capabilities of human monocytes correlates with their expression of HLA-DS, an Ia determinant distinct from HLA-DR. J Immunol 130:706–711, 1983

  51. 51.

    Knowles DM II, Toldijan B, Marboe C, D'Agati V, Grimes M, Chess L: Monoclonal anti-human monocyte antibodies OKM1 and OKM5 possess distinctive tissue distributions including differential reactivity with vascular endothelium. J Immunol 132:2170–2173, 1984

  52. 52.

    Bensussan A, Meuer SC, Schlossman SF, Reinherz EL: Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with T cell clones. J Exp Med 159:559–576, 1984

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Moreno, J., Lipsky, P.E. Functional heterogeneity of human antigen-presenting cells: Presentation of soluble antigen but not self-Ia by monocytes. J Clin Immunol 6, 9–20 (1986). https://doi.org/10.1007/BF00915359

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Key words

  • Antigen presentation
  • autologous mixed lymphocyte reaction
  • monoclonal antibodies
  • monocytes