Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4(+) perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype

Walton, J.A., Lydyard, P.M., Nathwani, A., Emery, V., Akbar, A., Glennie, M.J. and Porakishvili, N. 2010. Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4(+) perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype. British Journal of Haematology. 148 (2), pp. 274-284.

TitlePatients with B cell chronic lymphocytic leukaemia have an expanded population of CD4(+) perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype
AuthorsWalton, J.A., Lydyard, P.M., Nathwani, A., Emery, V., Akbar, A., Glennie, M.J. and Porakishvili, N.
Abstract

Summary - We have previously shown an expansion of cytotoxic antigen-experienced CD4(+)T cells (CTLs) that express perforin (PF) in the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B-CLL). Increased frequencies of CD4(+)CTLs have since been attributed to chronic viral infections, particularly, human cytomegalovirus (HCMV). The present study examined the involvement of CD4(+)CTLs in responses to HCMV in B-CLL, and characterized their differentiation. We studied 36 HCMV seropositive (SP) and seronegative B-CLL patients and 20 healthy age-matched individuals. The HCMV reactivity of CD4(+)PF(+) and CD4(+)PF(-) cells was determined by interferon-gamma expression, and expression of CD45RA and CCR7 was assessed by flow cytometry. Fluorescence in-situ hybridization was used to measure relative telomere lengths. CD4(+)PF(+)T cell expansion in B-CLL patients and controls was strongly associated with HCMV seropositivity. CD4(+)PF(+) compared to CD4(+)PF(-) cells from SP B-CLL patients elicited major histocompatibility complex (MHC) class II-restricted responses to HCMV. CD4(+)PF(+)T cells from patients and controls were enriched with highly differentiated T-effector/memory (CCR7(-)) and revertant (CCR7(-)CD45RA(+)) phenotype. CD4(+)PF(+)T cells from B-CLL patients had shorter telomeres than CD4(+)PF(-)T cells, indicating an extensive replicative history. We conclude that persistent exposure to HCMV antigens in SP B-CLL patients leads to an expansion of the circulating MHC class II-restricted CD4(+)PF(+)T cell population with effector/memory phenotype.

JournalBritish Journal of Haematology
Journal citation148 (2), pp. 274-284
ISSN0007-1048
Year29 Jan 2010
PublisherWiley
Digital Object Identifier (DOI)doi:10.1111/j.1365-2141.2009.07964.x
Publication dates
Published29 Jan 2010

Related outputs

Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine
Porakishvili, N., Roitt, I.M., Lund, T., Delves, P.J., Justesen, J., Martensen, P., Chikadze, N. and Kvirkvelia, N. 2018. Investigation of factors influencing the immunogenicity of hCG as a potential cancer vaccine. Clinical & Experimental Immunology. 193 (1), pp. 73-83.

Correlation between the expression of CD32 and CD180 receptors on CLL cells and MEC1 cell line
Tsertsvadze, T., Mitskevich, N., Ghirdaladze, D. and Porakishvili, N. 2015. Correlation between the expression of CD32 and CD180 receptors on CLL cells and MEC1 cell line. Georgian Medical News. 3 (240), pp. 56-59.

Rewiring of sIgM-mediated intracellular signaling through theCD180 Toll-like receptor
Porakishvili, N., Vispute, K., Rajakaruna, N., Kulikova, N., Tsertsvadze, T., Nathwani, A., Damle, R.N., Clark, E.A., Rai, K.R., Chiorazzi, N. and Lydyard, P.M. 2015. Rewiring of sIgM-mediated intracellular signaling through theCD180 Toll-like receptor. Molecular Medicine. 21, pp. 46-57.

Cells, tissues and organs of the immune system
Lydyard, P.M. and Porakishvili, N. 2012. Cells, tissues and organs of the immune system. in: Male, D., Brostoff, J., Roth, D.B. and Roitt, I.M. (ed.) Immunology (8th edition) Elsevier. pp. 17-50

CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells
Porakishvili, N., Memon, A., Vispute, K., Kulikova, N., Clark, E.A., Rai, K.R., Nathwani, A., Damle, R.N., Chiorazzi, N. and Lydyard, P.M. 2011. CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells. British Journal of Haematology. 153 (4), pp. 486-498.

Antibodies against hCG in patients with gynecological tumors
Chikadze, N., Akhvlediani, L., Gachechiladze, N., Delves, P.J. and Porakishvili, N. 2010. Antibodies against hCG in patients with gynecological tumors. in: Rafael, Z.B. (ed.) Proceedings of the 13th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) November 4-7, 2010 – Berlin (Germany) Monduzzi. pp. 187-192

Association between seropositivity for cytomegalovirus (CMV) and CD4+ cytotoxic T cells expansions in patients with B-cell Chronic Lymphocyte Leukaemia (B-CLL) and healthy controls
Kulikova, N., Amaglobeli, N., Tsertsvadze, T., Tsagareishvili, P., Sereda, L., Tevzadze, M., Kardava, L., Ghirdaladze, M., Gachechiladze, N., Lukhumaidze, M. and Porakishvili, N. 2009. Association between seropositivity for cytomegalovirus (CMV) and CD4+ cytotoxic T cells expansions in patients with B-cell Chronic Lymphocyte Leukaemia (B-CLL) and healthy controls. Proceedings of the Georgian Academy of Sciences. 7 (3-4), pp. 41-46.

Engagement of different Fc-gamma receptors in phagocytosis of immune complexes containing antibodies to mutated human chorionic gonadotropin β chain (hCG-beta) and native hCG molecule
Chikadze, N., Janikashvili, N., Gachechiladze, N., Lomishvili, N., Kvirkvelia, N., Delves, P.J. and Porakishvili, N. 2009. Engagement of different Fc-gamma receptors in phagocytosis of immune complexes containing antibodies to mutated human chorionic gonadotropin β chain (hCG-beta) and native hCG molecule. Proceedings of the Georgian Academy of Sciences. 7 (1-2), pp. 39-46.

Differential expression of CD180 and IgM by B-cell chronic lymphocytic leukaemia cells using mutated and unmutated immunoglobulin VH genes
Porakishvili, N., Kulikova, N., Jewell, A.P., Youinou, P.Y., Yong, K.L., Nathwani, A., Heelan, B., Duke, V., Hamblin, T.J., Wallace, P., Ely, P., Clark, E.A. and Lydyard, P.M. 2005. Differential expression of CD180 and IgM by B-cell chronic lymphocytic leukaemia cells using mutated and unmutated immunoglobulin VH genes. British Journal of Haematology. 131 (3), pp. 313-319.

B cell response to surface IgM cross-linking identifies different prognostic groups of B-chronic lymphocytic leukemia patients
Nedellec, S., Renaudineau, Y., Bordron, A., Berthou, C., Porakishvili, N., Lydyard, P.M., Pers, J.O. and Youinou, P.Y. 2005. B cell response to surface IgM cross-linking identifies different prognostic groups of B-chronic lymphocytic leukemia patients. Journal of Immunology. 174 (6), pp. 3749-3756.

Cytotoxic CD4+ T cells in patients with B cell chronic lymphocytic leukemia kill via a perforin-mediated pathway
Porakishvili, N., Kardava, L., Jewell, A.P., Yong, K.L., Glennie, M.J., Akbar, A. and Lydyard, P.M. 2004. Cytotoxic CD4+ T cells in patients with B cell chronic lymphocytic leukemia kill via a perforin-mediated pathway. Haematologica. 89 (4), pp. 435-443.

Patterns of the expression of CD32 and CD64 on monocytes of patients with B cell chronic lymphocytic leukaemia
Porakishvili, N. 2004. Patterns of the expression of CD32 and CD64 on monocytes of patients with B cell chronic lymphocytic leukaemia. Proceedings of the Georgian Academy of Sciences. 2 (3-4), pp. 86-91.

The role of complement in the clearance of human chorionic gonadotropin (HCG) containing immune complexes
Janikashvili, N., Chikadze, N., Gabunia, K. and Porakishvili, N. 2004. The role of complement in the clearance of human chorionic gonadotropin (HCG) containing immune complexes. Proceedings of the Georgian Academy of Sciences. 2 (3-4), pp. 92-96.

Impaired phagocytic function of monocytes in B cell chronic lymphocytic leukaemia
Akhobadze, T., Amaglobeli, N., Sereda, L., Shelegia, K., Lomishvili, N., Burjanadze, L., Ghirdaladze, D., Iosava, G. and Porakishvili, N. 2004. Impaired phagocytic function of monocytes in B cell chronic lymphocytic leukaemia. Bulletin of the Georgian Academy of Sciences. 169 (3), pp. 619-622.

The use of hepatitis B core antigen particles as a presentation scaffold for a peptide-based contraceptive vaccine
Kvirkvelia, N., Page, M., McBride, J.D., Porakishvili, N., Lund, T., Roitt, I.M. and Delves, P.J. 2003. The use of hepatitis B core antigen particles as a presentation scaffold for a peptide-based contraceptive vaccine. Journal of Reproductive Immunology. 58 (2), p. 138.

Activation of B-CLL cells by CD180 monoclonal antibodies: responders and non-responders
Porakishvili, N., Slovick, N., Jewell, A.P., Youinou, P.Y., Nathwani, A., Yong, K.L., Stevenson, F.K., Clark, E.A. and Lydyard, P.M. 2003. Activation of B-CLL cells by CD180 monoclonal antibodies: responders and non-responders. Blood. 102, p. 432a.

Preferential expression of CD180 by B cell chronic lymphocytic leukaemia (B-CLL) cells using IgVh mutated than those using IgVh unmutated genes
Porakishvili, N., Kulikova, N., Jewell, A.P., Youinou, P.Y., Yong, K.L., Nathwani, C., Heelan, B., Duke, V., Stevenson, F.K., Hamblin, T.J., Wallace, P., Ely, P., Clark, E.A. and Lydyard, P.M. 2003. Preferential expression of CD180 by B cell chronic lymphocytic leukaemia (B-CLL) cells using IgVh mutated than those using IgVh unmutated genes. Leukemia and Lymphoma. 44 (Supp. 2), p. S17.

Aberrant expression of Ccy-receptor (CD64) by monoclytes and neutrophils from patients with B cell chronic lymphocytic leukaemia
Porakishvili, N., Akhobadze, T., Kapanadze, T. and Baloyan, D. 2003. Aberrant expression of Ccy-receptor (CD64) by monoclytes and neutrophils from patients with B cell chronic lymphocytic leukaemia. Proceedings of the Georgain Academy of Sciences. 1 (1-2), pp. 39-42.

Assessment of in vitro phagocytosis of immune complexes containing native molecules of human chorionic gonadotropin (hCG) and mutant sera
Chikadze, N., Janikashvili, N. and Porakishvili, N. 2003. Assessment of in vitro phagocytosis of immune complexes containing native molecules of human chorionic gonadotropin (hCG) and mutant sera. Bulletin of the Georgian Academy of Sciences. 168 (2), pp. 373-376.

Immunogenicity and cross-reactivity of a novel mutant recombinant hCGb-protein
Chikadze, N., Janikashvili, N., Delves, P.J. and Porakishvili, N. 2003. Immunogenicity and cross-reactivity of a novel mutant recombinant hCGb-protein. Bulletin of the Georgian Academy of Sciences. 167 (3), pp. 558-562.

Elimination of luteinizing hormone cross-reactive epitopes from human chorionic gonadotropin
Porakishvili, N., Dalla Chiesa, M., Chikadze, N., Martensen, P., Justesen, J., Lund, T., Delves, P.J. and Roitt, I.M. 2002. Elimination of luteinizing hormone cross-reactive epitopes from human chorionic gonadotropin. Vaccine. 20 (16), pp. 2053-2059.

The role of IgE in the development of hypersensitivity in allergic and autoimmune conditions
Lomishvili, N., Mitskevichi, N., Amaglobeli, N. and Porakishvili, N. 2002. The role of IgE in the development of hypersensitivity in allergic and autoimmune conditions. Proceedings of the Georgian Academy of Sciences. 28, pp. 349-353.

Phagocytosis and the regulation of apoptosis in B-chronic lymphocytic leukaemia
Gabunia, K., Kardava, L., Kulikova, N., Jordania, T., Burjanadze, L., Sereda, L. and Porakishvili, N. 2002. Phagocytosis and the regulation of apoptosis in B-chronic lymphocytic leukaemia. Bulletin of the Georgian Academy of Sciences. 166 (1), pp. 153-157.

Expansion of CD4+ T cells with a cytotoxic phenotype in patients with B-chronic lymphocytic leukaemia (B-CLL)
Porakishvili, N., Roschupkina, T., Kalber, T., Jewell, A.P., Patterson, K., Yong, K.L. and Lydyard, P.M. 2001. Expansion of CD4+ T cells with a cytotoxic phenotype in patients with B-chronic lymphocytic leukaemia (B-CLL). Clinical and Experimental Immunology. 126 (1), pp. 29-36.

Recent progress in the understanding of B-cell functions in autoimmunity
Porakishvili, N., Mageed, R.A., Jamin, C., Pers, J.O., Kulikova, N., Renaudineau, Y., Lydyard, P.M. and Youinou, P.Y. 2001. Recent progress in the understanding of B-cell functions in autoimmunity. Scandinavian Journal of Immunology. 54 (1-2), pp. 30-38.

Refocusing of B-cell responses following a single amino acid substitution in an antigen
Dalla Chiesa, M., Martensen, P., Simmons, C., Porakishvili, N., Justesen, J., Dougan, G., Roitt, I.M., Delves, P.J. and Lund, T. 2001. Refocusing of B-cell responses following a single amino acid substitution in an antigen. Immunology. 103 (2), pp. 172-178.

The role of immune complexes in immunopathogenesis of extrinsic allergic alveolitis caused by the contact with organic dust
Mitskevichi, N., Machavarani, K., Khechinashvili, G. and Porakishvili, N. 2001. The role of immune complexes in immunopathogenesis of extrinsic allergic alveolitis caused by the contact with organic dust. Proceedings of the Georgian Academy of Sciences. 27, pp. 391-396.

Serum factors and T cell phenotype in patients with systemic lupus erythematosus (SLE), SLE-complicated with glomerulonephritis (SLE-GN) and in healthy controls
Lomishvili, N., Kalandadze, N. and Porakishvili, N. 2001. Serum factors and T cell phenotype in patients with systemic lupus erythematosus (SLE), SLE-complicated with glomerulonephritis (SLE-GN) and in healthy controls. Bulletin of the Georgian Academy of Sciences. 163 (3), pp. 233-236.

Autoantibodies to human chorionic gonadotropin in patients with systemic lupus erythematosus and patients with tumours of the reproductive systems
Lomishvili, N., Akhvlediani, L., Chikadze, N. and Porakishvili, N. 2001. Autoantibodies to human chorionic gonadotropin in patients with systemic lupus erythematosus and patients with tumours of the reproductive systems. Proceedings of the Georgian Academy of Sciences. 27, pp. 235-238.

Induction of apoptosis by anti-CD5 monoclonal antibodies in B-CLL cells correlates with the level of CD79b expression
Kulikova, N., Lydyard, P.M. and Porakishvili, N. 2001. Induction of apoptosis by anti-CD5 monoclonal antibodies in B-CLL cells correlates with the level of CD79b expression. Proceedings of the Georgian Academy of Sciences. 27, pp. 363-368.

Proliferation of B-chronic lymphocytic leukaemic cells in vitro in response to dihydroxycinnamate-derived polymers from symphytum asperum and symphytum caucasicum
Kardava, L., Tevzadze, M., Gabunia, K. and Porakishvili, N. 2001. Proliferation of B-chronic lymphocytic leukaemic cells in vitro in response to dihydroxycinnamate-derived polymers from symphytum asperum and symphytum caucasicum. Trans-Caucasian Journal of Immunology. 2, pp. 77-87.

The cell cycle progression of B-chronic lymphocytic leukaemia cells in vitro
Kardava, L., Kulikova, N., Tevzadze, M. and Porakishvili, N. 2001. The cell cycle progression of B-chronic lymphocytic leukaemia cells in vitro. Proceedings of the Georgian Academy of Sciences. 27, pp. 4-6.

CD5-induced apoptosis of B cells in some patients with chronic lymphocytic leukemia
Pers, J.O., Berthou, C., Porakishvili, N., Burdjanadze, N., Le Calvez, G., Abgrall, J.F., Lydyard, P.M., Youinou, P.Y. and Jamin, C. 2001. CD5-induced apoptosis of B cells in some patients with chronic lymphocytic leukemia. Leukemia. 16 (1), pp. 44-52.

Impaired phagocytic function of polymorpho-nuclear neutrophils in B chronic lymphocytic leukemia.
Gabunia, K., Gachechiladze, N., Burjanadze, L., Roschupkina, T., Baloyan, D., Kardava, L., Ghirdaladze, D., Iosava, G., Jewell, A.P., Lydyard, P.M. and Porakishvili, N. 2000. Impaired phagocytic function of polymorpho-nuclear neutrophils in B chronic lymphocytic leukemia. Haematologica. 85 (Supple), pp. 28-29.

Dysphoria and immune status in postpartum women
Hucklebridge, F., Smith, M.D., Clow, A., Evans, P., Glover, V., Taylor, A., Adams, D. and Lydyard, P.M. 1994. Dysphoria and immune status in postpartum women. Biological Psychology. 37 (3), pp. 199-206.

Permalink - https://westminsterresearch.westminster.ac.uk/item/903vz/patients-with-b-cell-chronic-lymphocytic-leukaemia-have-an-expanded-population-of-cd4-perforin-expressing-t-cells-enriched-for-human-cytomegalovirus-specificity-and-an-effector-memory-phenotype


Share this
Tweet
Email