Abstract
Accessory function of monocytes for T-cell activation was studied in patients with systemic lupus erythematosus (SLE). Nylon column-purified T cells alone were not activated to proliferate by stimulation with concanavalin A (Con A), but the addition of dish-adherent monocytes restored the T-cell response in a dose-dependent manner (accessory function). This accessory function is mediated by HLA-DR-positive monocytes. This accessory function of monocytes was markedly impaired in SLE patients. The dysfunction of monocytes was marked in an active stage of SLE but not in an inactive stage of SLE. Furthermore, SLE T cells were not fully activated with Con A in the presence of normal monocytes, suggesting that both monocyte and T-cell functions were impaired in SLE patients. The dysfunction of SLE monocytes was due to neither the development of suppressor monocytes nor the overproduction of prostaglandins, because SLE monocytes did not suppress the accessory function of normal monocytes and indomethacin did not restore the dysfunction of SLE monocytes. The percentage of HLA-DR-positive cells in a monocyte population was markedly decreased in active SLE patients and moderately decreased in inactive SLE patients. Thus, the impairment of accessory function of monocytes in SLE patients seems to be derived from a decrease in HLA-DR-positive monocytes. These results suggest that the dysfunction of HLA-DR-positive monocytes plays an important role in the pathogenesis of SLE.
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References
Smith HR, Steinberg AD: Autoimmunity-A perspective. Ann Rev Immunol 1:175–185, 1983
Blaese RM, Grayson J, Steinberg AD: Elevated immunoglobulin secreting cells in the blood of patients with active systemic lupus erythematosus: Correlation of laboratory and clinical assessment of disease activity. Am J Med 69:345–350, 1980
Sakane T, Steinberg AD, Green I: Studies of immune functions of patients with systemic lupus erythematosus. I. Failure of suppressor T cell activity related to impaired generation of, rather than response to, suppressor cells. Arth Rheum 21:657–664, 1978
Unanue ER: The regulatory role of macrophages in antigenic stimulation. 2. Symbiotic relationship between lymphocytes and macrophages. Adv Immunol 31:1–16, 1981
Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH: Defective reticuloendotheial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med 300:518–523, 1979
Linker-Israeli M, Bakka AC, Kitridou RC, Gendler S, Gillis S, Horwitz DA: Defective production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE). J Immunol 130:2651–2655, 1983
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth Rheum 25:1271–1277, 1982
Yamashita U, Hamaoka T: The requirement of Ia-positive accessory cells for the induction of hapten-reactive cytotoxic T lymphocytes in vitro. J Immunol 123:2637–2643, 1979
Harrison MR, Thurmond GB, Thomas GM: A simple and versatile harvesting device for processing radioactive label incorporated into and/or released from cells in microculture. J Immunol Methods 4:11–21, 1974
Lampson LA, Levy R: Two populations of Ia-like molecules on a human B cell. J Immunol 125:293–299, 1980
Markenson JA, Morgan JW, Lockshin MD, Joachim C, Winifield JB: Response of fractional cells from patients with systemic lupus erythematosus and normals to blast mitogen. Evidence for a suppressor population of monocytes. Proc Soc Exp Biol Med 158:5–9, 1978
Sønderstrup Hansen G, Rubin B, Sørensen SF, Svejgaard A: Importance of HLA-D antigens for the cooperation between human monocytes and T lymphocytes. Eur J Immunol 8:520–525, 1978
Shirakawa F, Yamashita U, Suzuki H: Decrease in HLA-DR-positive monocytes in patients with systemic lupus erythematosus (SLE). J Immunol 134:3560–3562, 1985
Scher MG, Beller DI, Unanue ER: Demonstration of a soluble mediator that induces exudates rich in Ia-positive macrophages. J Exp Med 152:1684–1698, 1980
Becker S: Interferons as modulators of human monocytemacrophages differentiation. I. Interferon-γ increases HLA-DR expression and inhibits phagocytosis of zymosan. J Immunol 132:1249–1254, 1984
Snyder DS, Beller DI, Unanue ER: Prostaglandins modulate macrophage Ia expression. Nature 299:163–165, 1982
Snyder DS, Unanue ER: Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production. J Immunol 129:1803–1805, 1982
Kelley VE, Roths JB: Increase in macrophage Ia expression in autoimmune mice: Role of the lpr gene. J Immunol 129:923–925, 1982
Lu CY, Unanue ER: Spontaneous T-cell lymphokine production and enhanced macrophage Ia expression and tumorcidal activity in MRL-lpr mice. Clin Immunol Immunopathol 25:213–222, 1982
Sherr DH, Heghinian KM, Benacerraf B, Dorf ME: Immune suppression in vivo with antigen-modified syngeneic cells. IV. Requirement for Ia+ adherent cells for induction. J Immunol 124:1389–1395, 1980
Yamashita U, Ono S, Nakamura H: The syngeneic mixed leukocyte reaction in mice. II. The I region control of suppressor T cell activity induced in the syngeneic mixed leukocyte reaction. J Immunol 128:1011–1019, 1982
de Vries JE, Caviles AP Jr, Bont WS, Mendelsohn J: The role of monocytes in human lymphocyte activation by mitogens. J Immunol 122:1099–1107, 1979
Okudaira K, Searles RP, Ceuppens JL, Goodwin JS, Williams RC: Anti-Ia reactivity in sera from patients with systemic lupus erythematosus. J Clin Invest 69:17–24, 1982
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Shirakawa, F., Yamashita, U. & Suzuki, H. Reduced function of HLA-DR-positive monocytes in patients with systemic lupus erythematosus (SLE). J Clin Immunol 5, 396–403 (1985). https://doi.org/10.1007/BF00915337
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DOI: https://doi.org/10.1007/BF00915337