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In vivo effects of T suppressor molecules : specificity and dose effects

University of British Columbia

The suppressor circuit and it's components have been studied extensively in this laboratory and others for the past ten years. This laboratory has produced factor-secreting hybridoma cells which are analogous to first-order T suppressor cells directed against the tumor P815 . A monoclonal antibody has been raised which recognizes a common portion of suppressor cells and factors. These tools are used in this study. It had been seen that when 20 µg A10F (factor secreted by A10, the Ts1 analogue) was injected into a mouse concurrently with P815, the suppression of the mouse's immune response was boosted. This led to increased tumor growth and accelerated death. However, when A10F was injected ten days prior to the mouse receiving P815, the opposite effect was seen. Mice had smaller tumors and longer survival times. This was not the contrasuppressive effect described by other laboratories, as the effect seen was not merely an abrogation of suppression, but rather enhancement of the immune response. The specificity and dose response of the effect was examined. This immune enhancement effect was not specific within the context of syngeneic tumor systems. It was found that the same effects were seen when P815 was replaced with L1210 or M-1, both also being H-2d tumors. In fact, L1210 was more sensitive to A10F than P815. There was some level of specificity to the enhancement effect. When A10F was replaced with Fd11F, a suppressor factor raised to ferredoxin, no effect was seen. Conversely, A10F did not produce the same effects as Fd11F in the ferredoxin system. Suppressor deletion therapy was used in both of these systems to confirm that suppressor cells were responsible for the effects seen. Dose response studies showed that the enhancement effect was dose dependent. Doses of A10F below 20 µg did not produce enhancement in the P815 system. Enhancement was seen with lower doses of A10F in the L1210 system, but the effect did decrease at the lower doses. A model is proposed for the data presented.

Text

2010-08-28

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http://hdl.handle.net/2429/27870

Microbiology and Immunology

University of British Columbia

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