Abstract
Previous studies have revealed that the reticulum cell sarcoma (RCS) of SJL/J (H-2s, IE-) mice express an "IE-like" stimulatory tumor- associated antigen, the expression of which is requisite for stimulating host T cells necessary for tumor growth. Herein, we present evidence that the predominant T cells raised in the syngeneic response to both spontaneous and transplantable RCS tumors are of the V beta 17a TCR clonotype. The V beta 17a+ clonotype of T cells has been shown to interact with IE allogeneic specificities. We demonstrate that all four characterized RCS-specific T cell hybridomas stained positively for the anti-V beta 17a mAb, KJ23a. Additionally, KJ23a, when added to cocultures of the T cell hybridomas and RCS tumors, inhibited the release of IL-2 by the hybridomas. Further, KJ23a was shown to markedly inhibit the proliferation of SJL/J T cells when cocultured with either spontaneous or transplantable RCS tumor cells. When analyzed by flow cytometry, the T cell blast population raised in response to both spontaneous and transplantable RCS were greater than 80% KJ23a+. These T cells were brightly stained by the anti-CD4 mAb, Gk1.5, and, therefore, represent class II-responsive T cells. In corroboration of the in vitro data, T cells derived from mesenteric lymph nodes of RCS tumor-bearing mice had likewise undergone a similar expansion of V beta 17a+, CD4+ T cells. Together, these results indicate that KJ23a+ T cells play an important and predominant role in the response of SJL/J mice to spontaneous RCS tumors and provide further suggestive evidence that the stimulatory antigen(s) on the RCS tumor is IE or an "IE-like" molecule. Significantly, the important role V beta 17a+ T cells play in the response to RCS suggests a potential therapeutic role for KJ23a mAb in the intervention and prevention of RCS tumors in SJL/J mice.
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Selected References
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