Regulatory and Conventional CD4+ T Cells Show Differential Effects Correlating with PD-1 and B7-H1 Expression after Immunotherapy

Journal of Immunology - Tập 180 Số 5 - Trang 2981-2988 - 2008
Kory L. Alderson1, Qing Zhou1, Vanessa Berner1, Danice Wilkins1, Jonathan M. Weiss2, Bruce R. Blazar3, Renhao Li1, Robert H. Wiltrout2, Doug Redelman4, William J. Murphy1
1Department of Microbiology and Immunology and
2‡Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; and
3§Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455
4†Department of Physiology and Cell Biology, University of Nevada, Reno, NV 89557;

Tóm tắt

Abstract Recently, our laboratory reported that secondary CD8+ T cell-mediated antitumor responses were impaired following successful initial antitumor responses using various immunotherapeutic approaches. Although immunotherapy stimulated significant increases in CD8+ T cell numbers, the number of CD4+ T cells remained unchanged. The current investigation revealed a marked differential expansion of CD4+ T cell subsets. Successful immunotherapy surprisingly resulted in an expansion of CD4+Foxp3+ regulatory T (Treg) cells concurrent with a reduction of conventional CD4+ T (Tconv) cells, despite the marked antitumor responses. Following immunotherapy, we observed differential up-regulation of PD-1 on the surface of CD4+Foxp3+ Treg cells and CD4+Foxp3− Tconv cells. Interestingly, it was the ligand for PD-1, B7-H1 (PDL-1), that correlated with Tconv cell loss after treatment. Furthermore, IFN-γ knockout (IFN-γ−/−) and IFN-γ receptor knockout (IFN-γR−/−) animals lost up-regulation of surface B7-H1 even though PD-1 expression of Tconv cells was not changed, and this correlated with CD4+ Tconv cell increases. These results suggest that subset-specific expansion may contribute to marked shifts in the composition of the T cell compartment, potentially influencing the effectiveness of some immunotherapeutic approaches that rely on IFN-γ.

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Journal of Immunology

Tập 180 Số 5

2981-2988

Thông tin tác giả