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Inhibition of human lymphocyte reactivity by plasma fibronectin in vitro
1Department of Pediatrics, University of Wisconsin, Madison.
Abstract:
The effect of purified human plasma fibronectin (FN) on the reactivity of human lymphocyte-rich mononuclear cells to mitogens and allogeneic cell interactions was studied. Concentrations of FN from 25 to 100 micrograms per 250 microL of culture consistently depressed phytohemagglutinin (PHA) responses. To exert an inhibitory effect, FN must be present within 20 hours after the addition of PHA to cells, and, therefore, it appears to interfere with early events in the transformation process. Increasing the concentration of PHA failed to reduce the inhibitory effect of FN, which suggests that the depressed response was not the result of FN-PHA complex formation, which would reduce the amount of mitogen available for stimulation. This possibility was supported by the finding that FN also inhibited the mixed lymphocyte response (MLR), in a reaction that was not dependent on the activity of soluble antigen or mitogen. In contrast, the stimulation of lymphocytes to undergo transformation that is induced by the nonlectin mitogen, sodium periodate, was unaffected by FN. Periodate-treated cells are, however, already stimulated to undergo transformation, prior to their exposure to FN. FN did not interfere with the activity of interleukin-2, nor did it indirectly regulate lymphocyte responses by modifying the production and/or effect of humoral regulatory factors released from the adherent accessory cells (macrophages). These studies show that FN is a potent immunosuppressive agent in vitro.
Insights
Human plasma fibronectin (FN) significantly suppresses lymphocyte reactivity to mitogens like phytohemagglutinin (PHA) and inhibits mixed lymphocyte responses (MLR). This immunosuppressive effect occurs early in lymphocyte activation, indicating FN
Area of Science:
- Immunology
- Cell Biology
Background:
- Fibronectin (FN) is a key extracellular matrix protein involved in cell adhesion and migration.
- Its role in modulating immune cell responses, particularly lymphocyte activation, requires further elucidation.
Purpose of the Study:
- To investigate the in vitro effects of purified human plasma fibronectin (FN) on human lymphocyte reactivity.
- To determine FN's impact on responses to mitogens and allogeneic cell interactions.
Main Methods:
- Human lymphocyte-rich mononuclear cells were cultured with varying concentrations of purified human plasma fibronectin (FN).
- Responses to phytohemagglutinin (PHA), sodium periodate, and mixed lymphocyte reactions (MLR) were assessed.
- Interleukin-2 activity and regulatory factors from accessory cells were evaluated.
Main Results:
- FN (25-100 micrograms/250 microL) consistently inhibited phytohemagglutinin (PHA)-induced lymphocyte transformation.
- Inhibition required FN presence within 20 hours of PHA addition, suggesting interference with early activation events.
- FN also suppressed the mixed lymphocyte response (MLR) but did not affect sodium periodate-induced lymphocyte transformation.
- FN did not impact interleukin-2 activity or regulatory factors from macrophages.
Conclusions:
- Purified human plasma fibronectin acts as a potent immunosuppressive agent in vitro.
- FN interferes with early lymphocyte activation pathways, particularly those triggered by lectin mitogens.
- These findings highlight FN's potential role in regulating immune responses.
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