CD58/LFA-3 and IL-12 provided by activated monocytes are critical in the in vitro expansion of CD56(+) T cells

Division of Blood and Marrow Transplantation, Stanford University, Palo Alto, California, United States
Cancer Immunology and Immunotherapy (Impact Factor: 3.94). 03/2001; 49(12):629-40. DOI: 10.1007/s002620000148
Source: PubMed


A small proportion of human CD3+ T lymphocytes are known to co-express CD56, an antigen usually restricted in its expression to natural killer (NK) cells. Whereas the in vivo function of CD3+ CD56+ T cells remains unknown, we and others have previously shown that both in vitro and in vivo, these cells can mediate a significantly greater degree of MHC-unrestricted cytotoxicitv against a variety of human tumor cells when compared to either CD3+ CD56- T cells or lymphokine activated killer (LAK) cells. While the mechanismns regulating the in vivo expansion of CD56+ T cells are not known, here we demonstrate the importance of CD2-mediated IL-12-dependent signals in the in vitro expansion of CD56+ T cells. Specifically, we show that activated monocytes provide a contact dependent factor (CD58/LFA-3) and a soluble factor (IL-12), both critical for the in vitro expansion of CD56+ T cells. The biological and therapeutic implications of these findings are discussed.

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    • "Most of these CIK cells (87%) are positive for CD3 and for one of the T-cell coreceptor molecules CD4 (37.4%) or CD8 (64.2%), respectively. IFN-γ, added at day 0, activates monocytes providing crucial signals to T cells via interleukin-12 (IL-12) and CD58 (LFA-3) to expand CD56+ cells [15]. After 14 days of culture, 37.7% of cells are CD3+CD8+CD56+. "
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    • "At the end of the culture, the CD3 + CD56 + cells, derived from CD3 + CD56 − cells, could expand by up to 1000-fold and gave the greatest cytotoxicity against various tumor cell targets, including K562 and B cell lymphoma cell lines, as compared to CD3 + CD56 − cells [9]. The expression of CD56 on these non-MHC-restricted effector T cells was found to be the result of IFN-γ-priming that induced the production of IL-12 by monocytes and the upregulation of CD58 (LFA- 3), both of which were demonstrated to be crucial for the expansion of CD56 + T cells [10]. Subsequently, this unique subset of non-MHC-restricted CD3 + CD56 + T cells was referred to as NK-like T cells since, similar to the NK cells, they do not require prior specific sensitization to induce the recognition of target cells. "
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    ABSTRACT: Tesis Univ. Granada. Departamento de Histología. Leída el 27 de octubre de 2008
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