Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell (DC) maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library of T cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

“…4). It is believed that GM-CSF exerts indirect effects on T cells, since the majority of resting T cells express the a but not b chain of the GM-CSF receptor and therefore may not be responsive to exogenous GM-CSF in this context [11]. Our study also indicates that the predominant effect of GM-CSF on T-cell immune responses is exerted through the increased presence of IL-12-secreting DC (Fig.…”

“…GM-CSF is released by a myriad of cell types including macrophages, endothelial cells, type II alveolar epithelial cells, and activated CD4 1 and CD8 1 T cells, in response to proinflammatory cytokines such as TNF-a, IL-1 and IL-6 [11]. GM-CSF can expand DC numbers and enhance their immunostimulatory capacity by increasing surface expression of MHC II and co-stimulatory molecules, such as CD40 and CD86, as well as augmenting the bactericidal functions of alveolar macrophages [12,13].…”

Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice

“…35 A number of clinical studies using GM-CSF as a vaccine adjuvant for the treatment of cancers have been performed. Unfortunately, contradictory results were observed: some studies showed the stimulation of immune responses, 36,37 whereas others showed the suppression of immune responses.…”

“…A similar result was reported with a long-lasting polyethylene glycol-modified GM-CSF causing the expansion of CD11b 1 CD11c 1 dendritic cells in vivo. 35,42,48 To delineate the possible cumulative effects of sequential stimulation, a comparison was made with 30 mg of GM-CSF given to mice as a single injection. Although the effects were much greater than those from one or two low (10 mg) daily doses, its inferiority in terms of breaking immune tolerance was evidenced when the levels of induced anti-HBsAg antibodies, CTLs and HBsAg-positive hepatocyte clearance were compared.…”

Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- MacrophageColony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles

“…Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to expand myeloid-derived dendritic cell (DC) populations (20,47), to augment antigeninduced humoral and cellular immune responses, and to affect the Th1/Th2 cytokine balance (45). It has been extensively used as an effective genetic and protein adjuvant to enhance immunogenicity of tumor and vaccine antigens (6,14,16,28,29,31,35,42,48,50,54,56).…”