Neem leaf glycoprotein matures myeloid derived dendritic cells and optimizes anti-tumor T cell functions.

Abstract

In an objective to find out an effective, nontoxic dendritic cell (DC) maturating agent for human use, CD14(+) monocytes were differentiated with GMCSF/IL-4 and matured with neem leaf glycoprotein (NLGP). NLGP matured DCs (NLGP-DCs) show upregulated expression of CD83, CD80, CD86, CD40 and MHCs, in a comparable extent of control, LPS. NLGP-DCs secrete high amount of IL-12p70 with low IL-10. NLGP upregulates the expression of crucial transcription factor, ikaros, indicating maturation towards DC1 phenotype. Increased expression of CD28 and CD40L on T cells following co-culture with NLGP-DCs was noticed to promote DC-T interactions. As a result, T cells secrete high amount of IFN gamma with low IL-4 and generates anti-tumor type 1 immune microenvironment. Such NLGP-DCs present carcinoembryonic antigen (CEA) effectively to T cells to increase T cell mediated cytotoxicity of CEA(+) tumor cells in vitro and in vivo. With emergence of the NLGP as a promising DC maturating agent, NLGP-DCs can be used as a candidate vaccine tool for antigen specific cancer immunotherapy.

• Authors: Shyamal Goswami, Anamika Bose, Koustav Sarkar, Soumyabrata Roy, Tathagata Chakraborty, Utpal Sanyal, Rathindranath Baral
• Journal: Vaccine (Vaccine) Vol. 28 Issue 5 Pg. 1241-52 (Feb 03 2010) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 19969119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, CD
• Glycoproteins
• Plant Proteins
• Interleukin-10
• Interleukin-12

Topics

• Animals
• Antigens, CD (immunology)
• Azadirachta
• Cell Line, Tumor
• Dendritic Cells (immunology)
• Female
• Glycoproteins (chemistry, isolation & purification, pharmacology)
• Humans
• Immunotherapy
• Interleukin-10 (immunology)
• Interleukin-12 (immunology)
• Mice
• Monocytes (immunology)
• Neoplasm Transplantation
• Neoplasms, Experimental (immunology, therapy)
• Plant Leaves
• Plant Proteins (chemistry, isolation & purification, pharmacology)
• T-Lymphocytes, Cytotoxic (immunology)
• Transplantation, Heterologous