Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy

Kory L. Alderson, Qing Zhou, Vanessa Berner, Danice E C Wilkins, Jonathan M. Weiss, Bruce R. Blazar, Lisbeth A. Welniak, Robert H. Wiltrout, Doug Redelman, William J Murphy

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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- +.

Original languageEnglish (US)
Pages (from-to)2981-2988
Number of pages8
JournalJournal of Immunology
Volume180
Issue number5
StatePublished - Mar 1 2008
Externally publishedYes

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Immunotherapy
T-Lymphocytes
Regulatory T-Lymphocytes
Up-Regulation
CD80 Antigens
T-Lymphocyte Subsets
Cell Count
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Alderson, K. L., Zhou, Q., Berner, V., Wilkins, D. E. C., Weiss, J. M., Blazar, B. R., ... Murphy, W. J. (2008). Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy. Journal of Immunology, 180(5), 2981-2988.

Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy. / Alderson, Kory L.; Zhou, Qing; Berner, Vanessa; Wilkins, Danice E C; Weiss, Jonathan M.; Blazar, Bruce R.; Welniak, Lisbeth A.; Wiltrout, Robert H.; Redelman, Doug; Murphy, William J.

In: Journal of Immunology, Vol. 180, No. 5, 01.03.2008, p. 2981-2988.

Research output: Contribution to journalArticle

Alderson, KL, Zhou, Q, Berner, V, Wilkins, DEC, Weiss, JM, Blazar, BR, Welniak, LA, Wiltrout, RH, Redelman, D & Murphy, WJ 2008, 'Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy', Journal of Immunology, vol. 180, no. 5, pp. 2981-2988.
Alderson KL, Zhou Q, Berner V, Wilkins DEC, Weiss JM, Blazar BR et al. Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy. Journal of Immunology. 2008 Mar 1;180(5):2981-2988.
Alderson, Kory L. ; Zhou, Qing ; Berner, Vanessa ; Wilkins, Danice E C ; Weiss, Jonathan M. ; Blazar, Bruce R. ; Welniak, Lisbeth A. ; Wiltrout, Robert H. ; Redelman, Doug ; Murphy, William J. / Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy. In: Journal of Immunology. 2008 ; Vol. 180, No. 5. pp. 2981-2988.
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