In Vitro Induction of Nonspecific Resistance in Macrophages by Specifically Sensitized Lymphocytes

Abstract

Experiments were carried out to determine whether macrophages can be activated in vitro to resist challenge with heterologous microorganisms. Sensitized spleen cells from guinea pigs chronically infected with Toxoplasma gondii were cultured with normal guinea pig peritoneal macrophages in the presence and absence of Toxoplasma antigen. Macrophage monolayers incubated with sensitized spleen cells and antigen were markedly resistant to challenge from Listeria monocytogenes . Resistance was manifested by prolonged survival of the monolayers and rapid intracellular killing of the bacteria. Macrophages incubated with sensitized spleen cells but in the absence of antigen, as well as macrophages cultured with normal spleen cells, in the presence or absence of antigen, were rapidly destroyed. Sensitized spleen cells responded to the presence of Toxoplasma antigen by increased uptake of tritium-labeled thymidine. Supernatant fluid medium obtained from cultures of macrophages, sensitized spleen cells, and antigen contained a macrophage migration inhibitory factor(s). In addition, these supernatant fluids were capable of inducing increased resistance to Listeria in normal macrophages.

Cell-Mediated Immunity Against Besnoitia and Toxoplasma in Specifically and Cross-Immunized Hamsters and in Cultures

“…Some investigators have emphasized the nonspecific resistance displayed against some intracellular pathogens. Cellular cross-resistance has been studied in mice infected with Besnoitia or Toxoplasma which were challenged with unrelated organisms (33) and has been observed in cell culture using Listeria as a measure of resistance (34). However, Listeria is so vulnerable to activated macrophages that it may not be suitable to measure the higher levels of immunity required in more persistent infections.…”

“…That direct microbicidal enhancing activity was inseparable from MIF was claimed (32,34) and then rejected when MIF-containing supernatants did not produce microbicidal effects in normal cultured macrophages (41). Youmans and collaborators (42)(43)(44) have been able to separate MIF from another soluble factor which inhibits intracellular mycobacterial growth, and presumably derived from two subsets of thymus-derived lymphocytes: one affecting delayed hypersensitivity, another microbicidal function (42).…”

T Cell Response to Viral and Bacterial Infection

“…For example, does the same individual sensitized T cell produce a variety of molecular mediators (W.H.O. 1973), activate macrophages to increased bactericidal ability (Simon & Sheagren 1971, Krahenbuhl & Remington 1971, arm macrophages to kill tumour cells (Evans et al 1972), help (Claman et al 1966, Davies 1969, Miller & Mitchell 1969, Miller et al 1971 or suppress (Allison et al 1971, Gershon & Kondo 1971 antibody responses? Or is there functional restriction as in B cells producing particular classes of immunoglobulin?…”

“…For 2 to 3 days the bacteria grow within the mononuclear phagocytes which populate the lesions; recovery from infection therefore depends upon improvement of the bactericidal ability of these macrophages (Mackaness 1962). This process appears to be T cell-dependent (Lane & Unanue 1972, Blanden & Langman 1972, North 1973a, the most likely explanation being the production of soluble 'macrophage-activating factors' by sensitized T cells stimulated by antigen (Simon & Sheagren 1971, Krahenbuhl &. Remington 1971.…”

Neutrophils are involved in the non‐specific resistance to listeriosis induced by mycobacterial infections

“…[2][3][4][5][6][7] The activated T cells will then secrete cytokines that will activate the mononuclear phagocytes turning them into cells with potent antimicrobial activity. [8][9][10][11] The antimicrobial activity of the macrophages is, however, non-specific in nature since it is able to lead to the control of not only the inducer micro-organism but is also effective against heterologous microbes with unrelated antigenic specificities. [12][13][14] This phenomenon has been called non-specific resistance and has been attributed to the action of activated macrophages.…”