Secretion of a macrophage‐activating factor distinct from interferon‐γ by human T cell clones

Experimental studies have suggested that antigen-specific T lymphocytes are important mediators of resistance to infection with the pathogenic fungus Histoplasma capsulation. To gain a better understanding of the role of T lymphocytes, we developed murine T-cell lines and clones that recognized Histoplasma antigens. These T cells were of the helper/inducer phenotype (Thy-1.2+ Lyt-1+ L3T4+ Lyt-2-) and exerted multiple immunological functions. T-cell lines and 12 clones proliferated vigorously in response to histoplasmin; the T-cell lines and 6 clones also were reactive with heterologous fungal antigens prepared from either Blastomyces dermatitidis or Coccidioides immitis. Recognition of antigen by T cells was H-2 restricted; in the absence of antigen, four clones demonstrated alloreactivity. All T-cell clones conferred local delayed-type hypersensitivity responses when injected with antigen into footpads of mice. Ten of 12 T-cell clones released interleukin-2 after stimulation with antigen, and all clones tested secreted interferon. Moreover, culture supernatants from antigen-stimulated clones armed peritoneal macrophages to inhibit intracellular growth of H. capsulatum yeast cells. All clones assayed exerted nonspecific help. Thus, development of T-cell clones should facilitate analysis of the regulatory properties of Histoplasma-specific T cells.

Section: Discussionmentioning

confidence: 99%

Development and characterization of Histoplasma capsulatum-reactive murine T-cell lines and clones

Deepe¹,

Smith²,

Sonnenfeld³

et al. 1986

“…It seems likely that a number of factors are responsible for macrophage activation, and it has been demonstrated that T-cell products contain macrophage-activating potential even after treatment with monoclonal antibodies to IFN-y (1). Thus, it may be that the various methods of activating or eliciting macrophages used in this study have different effects on the ability of the cell to respond to IFN--y. Macrophage activation is thought to involve a number of events (4, 6, 7), and it may be that thioglycolate treatment predisposes macrophages to respond to IFN, whereas the other treatments do not.…”

mentioning

confidence: 89%

Effect of gamma interferon on hydrogen peroxide production by cultured mouse peritoneal macrophages

Sharp¹,

Banerjee²

1986

Macrophage activation is thought to be mediated via a number of T-lymphocyte products, including gamma interferon (IFN-,y). However, our studies indicate that IFN--y acts as a regulator molecule rather than solely as an activator. This depends upon the status of the macrophage. IFN-,y treatment of resting macrophages and those activated or elicited by sodium caseinate, lipopolysaccaride, or Mycobacterium bovis BCG did not result in activation, as measured by hydrogen peroxide production; however, when thioglycolate was used as an eliciting agent, incubation with IFN--y resulted in a dramatic increase in hydrogen peroxide production compared with that by untreated controls.

“…r-IFN--y has been shown to activate macrophages in vitro (21) and also to enhance macrophage functions when administered in vivo (13). Our native lymphokine preparations certainly contain IFN--y, but there is also increasing evidence for the existence of macrophage-activating molecules distinct from IFN--y (1).…”

Section: Resultsmentioning

confidence: 96%

Liver macrophages (Kupffer cells) as cytotoxic effector cells in extracellular and intracellular cytotoxicity

Decker¹,

Kiderlen²,

Lohmann‐Matthes³

1985

The potential of the resident murine Kupffer cell to be cytotoxic in extra- and intracellular killing systems in vitro was investigated. Kupffer cells exerted no spontaneous cytotoxicity but were readily susceptible to activation with lymphokines. Such activated Kupffer cells very efficiently killed extracellular P815 cells and intracellular Leishmania spp. parasites. Kupffer cells could be induced to proliferate in vitro under the influence of colony-stimulating factor (D.-M. Chen, H.-S. Lin, P. Stahl, and R. Stanley, Exp. Cell Res. 121:103-109, 1979). Kupffer cell-derived macrophages cultured in vitro were identical to their liver-derived progenitors in terms of macrophage-specific surface antigens and with respect to extra- and intracellular cytotoxicity. These results demonstrated that Kupffer cells have a strong self-renewing potential and that essential Kupffer cell properties like antigenic determinants and cytotoxic potential remained stable throughout the replicative process. The possibility of Kupffer cell self-renewal in the intact organism is also discussed.