TACI mutation with invasive polyclonal CD8+ T-cell lymphoproliferation in a patient with common variable immunodeficiency Lucinda J. Berglund, MBBS,

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TACI mutation with invasive polyclonal CD8+ T-cell lymphoproliferation in a patient with common variable immunodeficiency Lucinda J. Berglund, MBBS, Graham J. Jones, BSc, PhD, Rajmohan Murali, MBBS, David A. Fulcher, MBBS, PhD Journal of Allergy and Clinical Immunology Volume 117, Issue 4, Pages 870-877 (April 2006) DOI: 10.1016/j.jaci.2006.01.004 Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 CD8+ T-cell infiltration of tissues stained with hematoxylin and eosin (A, C, and E) and with CD8 immunoperoxidase (B, D, and F). A and B: Spleen. Lymphoid aggregates composed of small to medium-sized CD8+ lymphoid cells. C and D, Liver. Dense CD8+ lymphoid infiltrate in portal tract (upper right), spilling over into the adjacent hepatic parenchyma. E and F: Kidney. Diffuse interstitial CD8+ lymphoid infiltrate with fibrous crescent in glomerulus on the left. Journal of Allergy and Clinical Immunology 2006 117, 870-877DOI: (10.1016/j.jaci.2006.01.004) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Flow cytometry of spleen cells showing expression of T-cell markers (left histograms, gated on lymphocytes by light scatter) and activation markers (right histograms, gated on T lymphocytes). Lymphocytes express all mature T-cell markers and are predominantly CD8+. T cells express the activation markers CD38 and HLA-DR but minimal expression of the other activation markers. Isotype controls are represented by dotted lines. PE, Phycoerythrin; FITC, fluorescein isothiocyanate; PC5, phycoerythrin-cyanin 5. Journal of Allergy and Clinical Immunology 2006 117, 870-877DOI: (10.1016/j.jaci.2006.01.004) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 C104R heterozygous mutation in TACI gene exon 3. The T to C mutation in the sense strand is indicated, and the codon triplet is boxed. Exons were amplified by means of PCR, with primers described in Salzer et al2 and sequenced with ABI Big Dye Version 3.1 (Applied Biosystems, Foster City, Calif) and an ABI Prism 3100 Genetic Analyser. Journal of Allergy and Clinical Immunology 2006 117, 870-877DOI: (10.1016/j.jaci.2006.01.004) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Speculative mechanism for the pathogenesis of CVID in the setting of the TACI mutation on the basis of experiments reported by Castigli et al.1 TACI engagement seems important for B-cell isotype switching to IgA, although it is unclear why IgG production is affected in patients with CVID because BAFF-R engagement appears sufficient to promote IgG production in vitro (see text). APC, Antigen-presenting cell. Journal of Allergy and Clinical Immunology 2006 117, 870-877DOI: (10.1016/j.jaci.2006.01.004) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions