ヒト末梢血Ｔ細胞活性化におけるＣＤ４４分子の関与

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  • Co-stimulatory Effects of CD44 on the Proliferative Responses of T Lymphocytes.

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In this study, we investigated whether CD 44 molecules expressed on T lymphocytes may have co-stimulatory effects on proliferative responses of peripheral blood T lymphocytes (PBT). When anti-CD 44 monoclonal antibodies (mAbs) were added to the culture in soluble form, the added mAbs did not alter the proliferative responses of PBT stimulated with immobilized anti-CD 3 mAb. However, when anti-CD 44 mAb were plate-coated together with anti-CD 3 mAb, the proliferation of the PBT was significantly augmented, as compared to stimulation with only anti-CD 3 mAb. In addition, pretreatment of PBT with mouse anti-CD 44 mAb and then anti-mouse immunoglobulin Ab clearly augmented the PBT proliferation. These results strongly suggest that cross-linking of CD 44 molecules on T lymphocytes is essential to costimulatory signal transduction for T lymphocyte activation. Furthermore, (immobilized hyaluronate HA), a natural ligand for CD 44, also increased anti-CD 3 mAb-induced PBT proliferation and this proliferation was specifically inhibited by anti-CD 44 mAb. These results imply that proliferation of PBT can be upregulated when CD 44 on the PBT interact with HA. In contrast, anti-VLA integrin mAbs did not induce significantly increased PBT proliferation, suggesting that CD 44 might function as co-stimulatory molecules for T lymphocyte activation more effectively than VLA integrins. Interestingly, it was also revealed that co-stimulation via CD 44 drastically increased IL-2 production. Moreover, analysis utilizing semiquantitative Reverse Transcription-Polymerase Chain Reaction (RTPCR) demonstrated that PBT co-stimulated with CD 44 induced rapid and marked messenger RNA expression of not only IL-2 but also interferon y and IL-4. The present results suggest that CD 44 may play important roles not only in functioning as an extracellular matrix receptor but also in the regulation of T lymphocyte proliferation when adhering to HA.

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