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Effects of K-76COOH (MX-1) on immune response: induction of suppressor T-cells by MX-1
11st Department of Pathology, Kansai Medical University, Osaka, Japan.
Abstract:
K-76COOH (MX-1), isolated from the cultured supernatant of a species of fungi imperfecti, Stachybotrys complement nov. sp. K-76, is an inhibitor of the complement component, C5. The effects of MX-1 on various immune responses were investigated. MX-1 enhanced the response of spleen cells to PHA and LPS: MX-1 at 0.01-250 micrograms/ml for PHA and at 10-250 micrograms/ml for LPS. In contrast, it inhibited the response to Con A: MX-1 at 0.01-500 micrograms/ml for spleen cells and at 100-500 micrograms/ml for thymocytes. MX-1 and IL-1 synergistically acted to enhance the Con A response of spleen and thymus cells from which accessory cells and Ia-positive cells had been removed by passing through Sephadex G-10 columns and treating with anti-Ia monoclonal antibody plus complement. T-cells pretreated with MX-1, IL-1 and Con A for 3 days suppressed not only the response of B-cells to LPS but also the production of anti-SRBC antibodies. In addition, MX-1 was found to increase CD8+ T-cells. These results suggest that MX-1 acts on T-cells to induce suppressor T-cells.
Insights
K-76COOH (MX-1), a complement C5 inhibitor, modulates immune responses by enhancing spleen cell reactions to PHA and LPS while inhibiting Con A responses. It also induces suppressor T-cells, impacting B-cell activity and antibody production.
Area of Science:
- Immunology
- Pharmacology
Background:
- K-76COOH (MX-1) is derived from fungi imperfecti, Stachybotrys complement nov. sp. K-76.
- MX-1 functions as an inhibitor of the complement component C5.
Purpose of the Study:
- To investigate the effects of MX-1 on various immune responses.
- To elucidate the role of MX-1 in T-cell and B-cell interactions.
Main Methods:
- Assessing spleen and thymus cell responses to PHA, LPS, and Con A in the presence of MX-1.
- Utilizing Sephadex G-10 column separation and anti-Ia monoclonal antibody treatment to isolate specific cell populations.
- Evaluating the impact of MX-1 and IL-1 on T-cell mediated suppression of B-cell responses and antibody production.
Main Results:
- MX-1 enhanced spleen cell responses to PHA and LPS.
- MX-1 inhibited spleen cell and thymocyte responses to Con A.
- MX-1 and IL-1 synergistically enhanced Con A response in accessory and Ia-positive cell-depleted populations.
- MX-1, IL-1, and Con A pretreated T-cells suppressed B-cell responses and antibody production.
- MX-1 increased CD8+ T-cells.
Conclusions:
- MX-1 modulates immune cell responses, with differential effects on PHA, LPS, and Con A stimulation.
- MX-1, in conjunction with IL-1, plays a role in T-cell activation and suppression.
- Evidence suggests MX-1 induces T-cells with suppressor activity, impacting B-cell function and antibody synthesis.