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Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis.
J Immunol. 2013 Dec 15; 191(12):5867-74.JI

Abstract

Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to characterize the immunological reconstitution of T cell subsets and its contribution to the prolonged RRMS suppression following alemtuzumab-induced lymphocyte depletion. The study was performed on blood samples from RRMS patients enrolled in the CARE-MS II clinical trial, which was recently completed and led to the submission of alemtuzumab for U.S. Food and Drug Administration approval as a treatment for RRMS. Alemtuzumab-treated patients exhibited a nearly complete depletion of circulating CD4(+) lymphocytes at day 7. During the immunological reconstitution, CD4(+)CD25(+)CD127(low) regulatory T cells preferentially expanded within the CD4(+) lymphocytes, reaching their peak expansion at month 1. The increase in the percentage of TGF-β1-, IL-10-, and IL-4-producing CD4(+) cells reached a maximum at month 3, whereas a significant decrease in the percentages of Th1 and Th17 cells was detected at months 12 and 24 in comparison with the baseline. A gradual increase in serum IL-7 and IL-4 and a decrease in IL-17A, IL-17F, IL-21, IL-22, and IFN-γ levels were detected following treatment. In vitro studies have demonstrated that IL-7 induced an expansion of CD4(+)CD25(+)CD127(low) regulatory T cells and a decrease in the percentages of Th17 and Th1 cells. In conclusion, our results indicate that differential reconstitution of T cell subsets and selectively delayed CD4(+) T cell repopulation following alemtuzumab-induced lymphopenia may contribute to its long-lasting suppression of disease activity.

Authors+Show Affiliations

Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24198283

Citation

Zhang, Xin, et al. "Differential Reconstitution of T Cell Subsets Following Immunodepleting Treatment With Alemtuzumab (anti-CD52 Monoclonal Antibody) in Patients With Relapsing-remitting Multiple Sclerosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 191, no. 12, 2013, pp. 5867-74.
Zhang X, Tao Y, Chopra M, et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013;191(12):5867-74.
Zhang, X., Tao, Y., Chopra, M., Ahn, M., Marcus, K. L., Choudhary, N., Zhu, H., & Markovic-Plese, S. (2013). Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. Journal of Immunology (Baltimore, Md. : 1950), 191(12), 5867-74. https://doi.org/10.4049/jimmunol.1301926
Zhang X, et al. Differential Reconstitution of T Cell Subsets Following Immunodepleting Treatment With Alemtuzumab (anti-CD52 Monoclonal Antibody) in Patients With Relapsing-remitting Multiple Sclerosis. J Immunol. 2013 Dec 15;191(12):5867-74. PubMed PMID: 24198283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. AU - Zhang,Xin, AU - Tao,Yazhong, AU - Chopra,Manisha, AU - Ahn,Mihye, AU - Marcus,Karen L, AU - Choudhary,Neelima, AU - Zhu,Hongtu, AU - Markovic-Plese,Silva, Y1 - 2013/11/06/ PY - 2013/11/8/entrez PY - 2013/11/8/pubmed PY - 2014/2/19/medline SP - 5867 EP - 74 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 191 IS - 12 N2 - Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to characterize the immunological reconstitution of T cell subsets and its contribution to the prolonged RRMS suppression following alemtuzumab-induced lymphocyte depletion. The study was performed on blood samples from RRMS patients enrolled in the CARE-MS II clinical trial, which was recently completed and led to the submission of alemtuzumab for U.S. Food and Drug Administration approval as a treatment for RRMS. Alemtuzumab-treated patients exhibited a nearly complete depletion of circulating CD4(+) lymphocytes at day 7. During the immunological reconstitution, CD4(+)CD25(+)CD127(low) regulatory T cells preferentially expanded within the CD4(+) lymphocytes, reaching their peak expansion at month 1. The increase in the percentage of TGF-β1-, IL-10-, and IL-4-producing CD4(+) cells reached a maximum at month 3, whereas a significant decrease in the percentages of Th1 and Th17 cells was detected at months 12 and 24 in comparison with the baseline. A gradual increase in serum IL-7 and IL-4 and a decrease in IL-17A, IL-17F, IL-21, IL-22, and IFN-γ levels were detected following treatment. In vitro studies have demonstrated that IL-7 induced an expansion of CD4(+)CD25(+)CD127(low) regulatory T cells and a decrease in the percentages of Th17 and Th1 cells. In conclusion, our results indicate that differential reconstitution of T cell subsets and selectively delayed CD4(+) T cell repopulation following alemtuzumab-induced lymphopenia may contribute to its long-lasting suppression of disease activity. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/24198283/Differential_reconstitution_of_T_cell_subsets_following_immunodepleting_treatment_with_alemtuzumab__anti_CD52_monoclonal_antibody__in_patients_with_relapsing_remitting_multiple_sclerosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=24198283 DB - PRIME DP - Unbound Medicine ER -