Mycoplasma-dependent activation of normal mouse lymphocytes: requirement for functional T lymphocytes in the cytotoxicity reaction mediated by Mycoplasma arthritidis

Abstract

Syngeneic and allogeneic target cells were killed in the presence of CBA mouse lymphocytes and viable Mycoplasma arthritidis. Medium supplementation had no effect on the response. Nonviable M. arthritidis was also capable of stimulating lymphocytotoxicity, although to a much lesser extent. Cytotoxicity was shown to be largely dependent upon the lymphocytes, since lymphocytes preincubated with mycoplasmas and treated to remove remaining organisms were highly toxic to target cells, whereas supernatants prepared from lymphocyte/mycoplasma mixtures exhibited minimal effects. A 6-h exposure of lymphocytes to mycoplasmas at a ratio of 100:1 was sufficient for commitment to target cell killing. Functional lymphocytes were required for the reaction, since y-irradiated lymphocytes did not develop cytotoxic potential despite the fact that the mycoplasmas replicated equally well in the presence of these and untreated lymphocytes. Furthermore, lymphocytes already activated with mycoplasmas lost cytotoxic potential after disruption. The kinetics and degree of lymphocytotoxicity induced by M. arthritidis and phytohemagglutinin toward 61Cr-labeled syngeneic fibroblasts were similar. Removal of most B cells and other adherent cells by column separation did not abrogate the cytotoxic effect. Lymphocyte suspensions treated with anti-Thy 1 antiserum and complement exhibited a marked decrease in their cytotoxic potential when added to labeled target cells in the presence of M. arthritidis. We conclude that the cytotoxic reaction is dependent upon the Tlymphocyte subpopulation. Mycoplasma arthritidis is a potent arthritogenic agent causing spontaneous or experimental arthritis in rats, mice, and rabbits (11, 13, 14, 22). We recently demonstrated that M. arthritidis exerts a mitogenic effect toward normal unsensitized mouse lymphocytes (10). Many other mycoplasma species appear to exhibit similar mitogenic properties (4, 10, 17, 20). We have also shown that M. arthritidis can induce normal mouse lymphocytes to exert a cytotoxic action on allogeneic and syngeneic mouse fibroblast target cells as evidenced by release of a '1C label (1). These observations are therefore of great interest in view of the intense inflamatory response and mononuclear cell reaction seen in the joints of animals infected with this organism.

Cell-mediated cytotoxicity against rat fibroblasts induced by Actinomyces viscosus

“…It is of particular interest that several recent studies that used Mycoplasma species to generate CMC against syngeneic fibroblasts have led to very similar results (1,13). In particular, Mycoplasma species have also been identified as B-cell mitogens (3,13,28), have been recognized as inducing the generation of cytotoxic lymphocytes requiring prolonged contact with syngeneic target cells for expression of cytotoxicity (14), and have been recognized as triggering the generation of cytotoxic lymphocytes after only brief exposure (13).…”

Cytotoxic cells induced after Chlamydia psittaci infection in mice

“…We observed that heated organisms tend to become stickier after treatment, and it is possible that sensitization with these organisms is due to nonspecific sticking to the cell surface. Mycoplasma arthritidis have been reported to sensitize cells to become cytotoxic effectors (7). It was suggested that the mycoplasmas, which bind to the surface of cells, may function as a glue, binding target cells to lymphocytes with preexisting cytotoxic potential.…”

Mycoplasma arginini TUH-14 membrane lipoproteins induce production of interleukin-1, interleukin-6, and tumor necrosis factor alpha by human monocytes

“…Indeed, mycoplasmas induce proliferation and immunoglobulin secretion of both resting and activated B lymphocytes (3,22,24). Various mycoplasma species behave as T-cell mitogens and induce the formation of cytotoxic T cells (6,17). Mycoplasma also induces macrophage-mediated cytolysis (10,30).…”