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Successful treatment of diabetic subjects with Fc-mutated, anti-CD3 mAb was associated with an expansion of CD8+ T-cells in peripheral blood. These cells had regulatory properties and expressed CTLA4 and FoxP3.
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Kremer J.M., Dougados M., Emery P., Durez P., Sibilia J., Shergy W., Steinfeld S., Tindall E., Becker J.C., Li T., et al. Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: twelve-month results of a phase iib, double-blind, randomized, placebo-controlled trial. Arthritis Rheum 52 (2005) 2263-2271. This and the following two papers demonstrate the use of costimulation blockade in patients with rheumatoid arthritis. Improvement in symptoms is accompanied by significant quality of life benefit as well as reduced joint damage.
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Autologous stem cell transplantation can provide long-term remission of juvenile idiopathic arthritis. This study demonstrates that treatment is associated with: homeostatic expansion of regulatory T-cells; production of naïve regulatory T-cells; and deviation of autoreactive cells from a pro-inflammatory to a regulatory phenotype.
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de Kleer I., Vastert B., Klein M., Teklenburg G., Arkesteijn G., Yung G.P., Albani S., Kuis W., Wulffraat N., and Prakken B. Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network. Blood 107 (2006) 1696-1702. Autologous stem cell transplantation can provide long-term remission of juvenile idiopathic arthritis. This study demonstrates that treatment is associated with: homeostatic expansion of regulatory T-cells; production of naïve regulatory T-cells; and deviation of autoreactive cells from a pro-inflammatory to a regulatory phenotype.
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A good review of the use of CAMPATH-1H in multiple sclerosis patients. A single course of treatment is associated with improvement in disability for up to 36 months.
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Coles A.J., Cox A., Le Page E., Jones J., Trip S.A., Deans J., Seaman S., Miller D.H., Hale G., Waldmann H., et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol 253 (2006) 98-108. A good review of the use of CAMPATH-1H in multiple sclerosis patients. A single course of treatment is associated with improvement in disability for up to 36 months.
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Cox A.L., Thompson S.A., Jones J.L., Robertson V.H., Hale G., Waldmann H., Compston D.A., and Coles A.J. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 35 (2005) 3332-3342
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A brief review of transplantation tolerance with an emphasis on 'almost tolerance'-where graft acceptance is maintained by a low, nontoxic dosage of maintenance immunosuppression, which may not be required indefinitely.
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Calne R.Y. Prope tolerance-the future of organ transplantation from the laboratory to the clinic. Int Immunopharmacol 5 (2005) 163-167. A brief review of transplantation tolerance with an emphasis on 'almost tolerance'-where graft acceptance is maintained by a low, nontoxic dosage of maintenance immunosuppression, which may not be required indefinitely.
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Larche M., and Wraith D.C. Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat Med 11 (2005) S69-S76. An excellent review of the state-of-the-art with respect to the use of synthetic peptide vaccines for the treatment of autoimmune and allergic diseases.
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This paper suggests that some of the effects of an HSP-derived peptide may reflect signalling through TLR-2 on T-cells. This results in increased adhesion and reduced chemotaxis, potentially reducing the trafficking of T-cells into inflamed tissues.
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Nussbaum G., Zanin-Zhorov A., Quintana F., Lider O., and Cohen I.R. Peptide p277 of HSP60 signals T cells: inhibition of inflammatory chemotaxis. Int Immunol 18 (2006) 1413-1419. This paper suggests that some of the effects of an HSP-derived peptide may reflect signalling through TLR-2 on T-cells. This results in increased adhesion and reduced chemotaxis, potentially reducing the trafficking of T-cells into inflamed tissues.
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Multiple, short, overlapping peptides derived from the major cat allergen, Fel d 1, were administered by intradermal injection to cat-allergic asthmatics. This was a small study (8 patients received peptide mixture and 8 placebo) but active treatment was associated with significant decreases in the late asthmatic reaction to whole cat dander as well as significant improvements in asthma quality of life scores. The next reference suggests that treatment may induce a T-cell population with specific regulatory/suppressor activity.
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Alexander C., Tarzi M., Larche M., and Kay A.B. The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy 60 (2005) 1269-1274. Multiple, short, overlapping peptides derived from the major cat allergen, Fel d 1, were administered by intradermal injection to cat-allergic asthmatics. This was a small study (8 patients received peptide mixture and 8 placebo) but active treatment was associated with significant decreases in the late asthmatic reaction to whole cat dander as well as significant improvements in asthma quality of life scores. The next reference suggests that treatment may induce a T-cell population with specific regulatory/suppressor activity.
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Suntharalingam G., Perry M.R., Ward S., Brett S.J., Castello-Cortes A., Brunner M.D., and Panoskaltsis N. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355 (2006) 1018-1028. The report of the devastating effects of a first-into-man study of a CD28 superagonist. Treatment was associated with a life-threatening cytokine storm in all recipients of active drug. This paper demonstrates the hazards inherent in translating pre-clinical findings of T-cell immunomodulators to the clinic.
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