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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2007

Open Access 01-12-2007 | Research

Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis

Authors: Francesca Chamian, Shao-Lee Lin, Edmund Lee, Toyoko Kikuchi, Patricia Gilleaudeau, Mary Sullivan-Whalen, Irma Cardinale, Artemis Khatcherian, Inna Novitskaya, Knut M Wittkowski, James G Krueger, Michelle A Lowes

Published in: Journal of Translational Medicine | Issue 1/2007

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Abstract

Background

Alefacept (anti-CD2) biological therapy selectively targets effector memory T cells (Tem) in psoriasis vulgaris, a model Type 1 autoimmune disease.

Methods

Circulating leukocytes were phenotyped in patients receiving alefacept for moderate to severe psoriasis.

Results

In all patients, this treatment caused a preferential decrease in effector memory T cells (CCR7- CD45RA-) (mean 63% reduction) for both CD4+ and CD8+ Tem, while central memory T cells (Tcm) (CCR7+CD45RA-) were less affected, and naïve T cells (CCR7+CD45RA+) were relatively spared. Circulating CD8+ effector T cells and Type 1 T cells (IFN-γ-producing) were also significantly reduced.

Conclusion

Alefacept causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis.
Appendix
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Literature
1.
Krueger JG: The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol. 2002, 46: 1-23. 10.1067/mjd.2002.120568.CrossRefPubMed
2.
Lew W, Bowcock AM, Krueger JG: Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and 'Type 1' inflammatory gene expression. Trends Immunol. 2004, 25 (6): 295-305. 10.1016/j.it.2004.03.006.CrossRefPubMed
3.
Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG: The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol. 1999, 113: 752-759. 10.1046/j.1523-1747.1999.00749.x.CrossRefPubMed
4.
Ellis CN, Krueger GG: Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. New England Journal of Medicine. 2001, 345 (4): 248-255. 10.1056/NEJM200107263450403.CrossRefPubMed
5.
Dustin ML, Springer TA: Role of lymphoctye adhesion receptors in transient interactions and cell locomotion. Annual Review of Immunology. 1991, 9: 27-66. 10.1146/annurev.iy.09.040191.000331.CrossRefPubMed
6.
Crawford K, Gabuzda D, Pantazopoulos V, Xu J, Clement C, Reinherz E, Alper CA: Circulating CD2+ monocytes are dendritic cells. J Immunol. 1999, 163: 5920-5928.PubMed
7.
Di Pucchio T, Lapenta C, Santini SM, Logozzi M, Parlato S, Belardelli F: CD2+/CD14+ monocytes rapidly differentiate into CD83+ dendritic cells. Eur J Immunol. 2003, 33: 358-367. 10.1002/immu.200310010.CrossRefPubMed
8.
Bacchmann MF: CD2 sets quantitative thresholds in T cell activation. Journal of Immunology. 1999, 190: 1383-1391.
9.
Miller GT, Hochman PS, Meier W, Tizard R, Bixler SA, Rosa MD, Wallner BP: Specific interaction of lymphocyte function associated antigen 3 with CD2 can inhibit T cell responses. Journal of Experimental Medicine. 1993, 178: 211-222. 10.1084/jem.178.1.211.CrossRefPubMed
10.
Lattine D, De La Parra B, Nizet Y, Cornet A, Giovino-Barry V, Monroy R, White-Schart ME, Bazin H: An-anti-CD2 mAb induces immunosuppresssion and hyporesponsiveness of CD2+ human T cells in vitro. International Immunology. 1995, 8: 1113-1119. 10.1093/intimm/8.7.1113.CrossRef
11.
Dumont C, Deas O, Mollereau B, Hebib C, Giovino-Barry V, Bernard A, Hirsch F, Charpentier B, Senik A: Potent apoptotic signaling and subsequent unresponsiveness induced by a sigle CD2 mAb (BTI-332) in activated human peripheral T cells. Journal of Immunology. 1998, 160: 3797-3804.
12.
van Kooyk Y, van de Weil-van Kemenade P, Weder P, Kuijers TW, Figdor CG: Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature. 1989, 342: 811-812. 10.1038/342811a0.CrossRefPubMed
13.
Majeau GR, Meier W, Jimmo B, Kioussis D, Hochman PS: Mechanisms of lymphocyte function-associated molecule 3-Ig fusion proteins inhibition of T cell responses. Structure/Function analysis in vitro and in human CD2 transgenic mice. Journal of Immunology. 1994, 152: 2753-2767.
14.
da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu Y-M, Hochman PS: Alefacept, and immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependant apoptosis of CD2+ cells. Journal of Immunology. 2002, 168: 4462-4471.CrossRef
15.
Sallusto F, Lenig D, RForster R, Lipp M, Lanzavecchia A: Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999, 401: 708-712. 10.1038/44385.CrossRefPubMed
16.
Sallusto F, Geginat J, Lanzavecchia A: Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004, 22: 745-763. 10.1146/annurev.immunol.22.012703.104702.CrossRefPubMed
17.
Hamann D, Baars PA, Rep MHG, Hooibrink B, JKertof-Garde SR, Klein MR, van Lier RAW: Phenotypic and functional separation of memory and effector human CD8+ T cells. Journal of Experimental Medicine. 1997, 186 (9): 1707-1418. 10.1084/jem.186.9.1407.CrossRef
18.
Gordon KB, Vaishnaw AK, O'Gorman J, Haney J, Menter A: Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory T-cell counts. Arch Dermatol. 2003, 139 (12): 1563-1570. 10.1001/archderm.139.12.1563.CrossRefPubMed
19.
Chamian F, Lowes MA, Lin SL, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG: Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci U S A. 2005, 102 (6): 2075-2080. 10.1073/pnas.0409569102.PubMedCentralCrossRefPubMed
20.
Haider AS, Lowes MA, Gardner H, Bandaru R, Darabi K, Chamian F, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Novitskaya I, Krueger JG: Novel insight into agonistic mechanism of alefacept in vivo: Differentially expressed genes may serve as biomarkers of response in psoriasis patients. J Immunol. 2007, 178 (11): 7442-9.CrossRefPubMed
21.
Gottlieb AB, Casale TB, Frankel E, Goffe B, Lowe N, Ochs HD, Roberts JL, Washenik K, Vaishnaw AK, Gordon KB: CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study. J Am Acad Dermatol. 2003, 49 (5): 816-825. 10.1016/S0190-9622(03)01836-X.CrossRefPubMed
22.
23.
Chavin KD, Lau HT, Bromberg JS: Prolongation of allograft and xenograft survival in mice by anti-CD2 monoclonal antibodies. Transplantation. 1992, 54: 286-291. 10.1097/00007890-199208000-00018.CrossRefPubMed
Metadata
Title
Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis
Authors
Francesca Chamian
Shao-Lee Lin
Edmund Lee
Toyoko Kikuchi
Patricia Gilleaudeau
Mary Sullivan-Whalen
Irma Cardinale
Artemis Khatcherian
Inna Novitskaya
Knut M Wittkowski
James G Krueger
Michelle A Lowes
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2007
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-5-27

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