| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Little, Elizabeth C. Rubinstein, Mark P. Bowers, Jacob S. Paulos, Chrystal M. Kundimi, Sreenath Huff, Logan W. Nelson, Michelle H. Schwartz, Kristina M. Thyagarajan, Krishnamurthy Cole, David J. Rogers, Carolyn E. Mehrotra, Shikhar |
| Description |
Author Affiliation: Nelson MH ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425); Kundimi S ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425); Bowers JS ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425); Rogers CE ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425); Huff LW ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425); Schwartz KM ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425); Thyagarajan K ( Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.); Little EC ( Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.); Mehrotra S ( Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.); Cole DJ ( Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.); Rubinstein MP ( Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425.); Paulos CM ( Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425) |
| Abstract |
The inducible costimulator (ICOS) plays a key role in the development of Th17 cells, but its role in the development and antitumor activity of IL-17-producing CD8(+) T cells (Tc17) remains unknown. We found that ICOS costimulation was important for the functional maintenance, but not differentiation, of Tc17 cells in vitro. Blocking the ICOS pathway using an antagonist mAb or by using recipient mice genetically deficient in the ICOS ligand reduced the antitumor activity of adoptively transferred Tc17 cells. Conversely, activating Tc17 cells with an ICOS agonist in vitro enhanced their capacity to eradicate melanoma and induce autoimmune vitiligo when infused into mice. However, ICOS stimulation did not augment the antitumor activity of IL-2 expanded T cells. Additional investigation revealed that ICOS stimulation not only increased IL-2R , CXCR3, and IL-23R expression on Tc17 cells, but also dampened their expression of suppressive molecule CD39. Although Tc17 cells activated with an ICOS agonist cosecreted heightened IL-17A, IL-9, and IFN-γ, their therapeutic effectiveness was critically dependent on IFN-γ production. Depletion of IL-17A and IL-9 had little impact on antitumor Tc17 cells activated with an ICOS agonist. Collectively, our work reveals that the ICOS pathway potentiates the antitumor activity of adoptively transferred Tc17 cells. This work has major implications for the design of vaccine, Ab and cell-based therapies for autoimmunity, infectious disease, and cancer. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1401082 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-02-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cd8-positive T-lymphocytes Immunology Immunotherapy, Adoptive Inducible T-cell Co-stimulator Protein Melanoma T-lymphocyte Subsets Animals Cell Differentiation Disease Models, Animal Enzyme-linked Immunosorbent Assay Flow Cytometry Interleukin-17 Lymphocyte Activation Mice Mice, Inbred C57bl Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
