Ex vivo induction and expansion of natural killer T cells by CD1d1-Ig coated artificial antigen presenting cells.
Natural killer T (NKT) cells play a pivotal role in maintaining immune homostasis. They recognize lipid antigen in the context of CD1d molecules and subsequently produce cytokines that activate cells of both the innate and adaptive immune responses. Many studies examining patients with autoimmune disease or cancer have shown that there is a reduction in both NKT cell number and function. Due to the complexities of manipulating NKT cells in vivo, ex vivo expanded effector NKT cells would be an excellent therapeutic modality. To date, immunotherapy utilizing the NKT/CD1d system has been dependent on the use of autologous DC in the presence or absence of a synthetic glycolipid, alpha-galactocylceramide. Here we report a novel technique that facilitates the growth and analysis of NKT cells through the use of CD1d-expressing aAPC. CD1d-based aAPC can effectively propagate both canonical (iNKT cells) and noncanonical (Valpha14(-)) NKT cells. Importantly, CD1d-Ig aAPC can expand NKT cells from cancer patients. Thus, CD1d-expressing aAPC will enhance our knowledge of NKT cell biology and could potentially be used as a novel tool in adoptive immunotherapeutic strategies.
Webb
Tonya J
TJ
Department of Pathology, Johns Hopkins School of Medicine, Ross Building Room 644S, Baltimore, MD 21205, USA. twebb5@jhmi.edu
Bieler
Joan G
JG
Schneck
Jonathan P
JP
Oelke
Mathias
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D002518:Ceramides / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D007136:Immunoglobulins / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000032:analysis; D055611:Natural Killer T-Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013997:Time Factors
D055610:Antigens, CD1d; C526877:CD1D protein, human; D017252:CD3 Complex; D002518:Ceramides; D016207:Cytokines; D007136:Immunoglobulins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell