PubMed · 2241030
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C Hauser. 1990. [Contact hypersensitivity. Cellular aspects].. https://pubmed.ncbi.nlm.nih.gov/2241030/
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We recently reported that HLA-G1-transfected antigen-presenting cells (HLA-G1+ APCs) were capable of inhibiting alloproliferative responses. The aim of the present work was to further study the function and the mechanisms of action of HLA-G1+ APCs. We show here that HLA-G1+ APCs are immunoinhibitory cells that (i) inhibit the proliferation of CD4+ T cells, (ii) shed HLA-G1 molecules that might provide extra, non-antigen-specific, inhibitory or proapoptotic signals, (iii) induce CD4+ T cell anergy, or at least long-term unresponsiveness, and (iv) cause the differentiation of CD4+ T cells into suppressive cells. Thus, HLA-G+ APCs might (i) be involved in the direct suppression of immune responses and (ii) contribute to long-term efficient immune escape or tolerance.
AIM: The prevention of recurrence of colon cancer (CC) after operation is very important for improvement of the prognosis of CC patients, especially those with micro-metastasis. The generation of fused cells between dendritic cells (DCs) and tumor cells maybe an effective approach for tumor antigen presentation in immunotherapy. In this study, we fused human colon caner SW480 cells and human peripheral blood - derived DCs to induce an antitumor activity against human CC. METHODS: CC SW480 cells and human peripheral blood - derived DCs were fused with 500 mL/L polyethylene glycol (PEG). RESULTS: The specific T cell responses activated by fusion cells (FCs), were observed. About 100 mL/L to 160 mL/L of the PEG-treated non-adherent cells with fluorescences were considered to be dendritomas that highly expressed the key molecules for antigen presentation in our five cases. In vitro studies showed that fusions effectively activated CD8(+) T lymphocytes to secrete interferon-gamma. The early apoptotic ratio of the colon cancer SW480 cells was higher than that of controls, which was affected by cytotoxic T lymphocytes (CTLs) stimulated by dendritomas. CONCLUSION: The data indicate that fusion of tumor cells with DCs is an attractive strategy to induce tumor rejection.
Dendritic cells (DCs) are the most potent of the antigen-presenting cells (APCs). Preparation of sufficient numbers of mature DCs, however, is both costly and time-consuming. We have examined here the possibility of using an alternative source of APCs that would be easier to obtain, would not require extensive culture, and thus would be more applicable to human immunotherapy protocols. We show here that freshly isolated human B cells can be efficiently infected by a replication-defective fowlpox recombinant vector, designated rF-TRICOM (TRIad of COstimulatory Molecules), to markedly increase surface expression of the human costimulatory molecule B7-1 and moderately increase expression of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-3 (LFA-3). Peptide-pulsed rF-TRICOM-infected B cells were highly efficient in activating antigen-specific human T cells and shown to be superior to the use of CD40L in enhancing APC potency. Moreover, when infection of freshly isolated B cells with rF-TRICOM was combined with CD40L, a still further marked enhancement of the antigen-presenting potency was observed. Ex vivo-generated antigen-specific T cells activated in this manner might be applied to experimental protocols or used for adoptive transfer in immunotherapy protocols.