Abstract
Patients with Wegener's granulomatosis have a high prevalence of expanded populations of CD4+ and CD8+ T cells bearing different α/β T cell receptors. To elucidate the role of these populations, we studied the phenotypic and functional characteristics of 13 expanded T cell populations in four patients for a period of 35–51 months. The expanded populations generally showed a persistently high expression of the activation markers HLA-DR and CD25. This expression was independent of the activity of the disease. The expanded populations also expressed CD45RO and/or CD45RA and most of them expressed CD57 but not CD28. Analysis of intracellular presence and secretion of IFN-γ, IL-2, and IL-4 showed that most of the expanded cell populations contained and/or secreted more of these cytokines than the nonexpanded populations, with an especially high expression/secretion of IFN-γ and IL-2. The expanded populations showed little proliferative response to Con A and OKT3. The proliferative response of the cells was partly restored after preincubation in medium alone. Some of the expanded populations were associated with disease activity, thus suggesting a link between expanded T cells and the disease. The activated status of the expanded populations and the tendency for certain populations to correlate in magnitude with disease activity suggest their involvement in the disease process. The relative stability of these cell populations indicates that the stimulus driving them is persistent, in agreement with the chronicity of the disease.
Similar content being viewed by others
REFERENCES
Wegener F: Uber eine eigenartige rhinogene Granulomatose mit besonderer Beteiligung des Arteriensystems und der Nieren. Pathol Anat 102:36–68, 1939
Godman GC, Churg J: Wegener's granulomatosis. AMA Arch Pathol 58:533–553, 1954
Giscombe R, Grunewald J, Nityanand S, Lefvert AK: T cell receptor (TCR) V gene usage in patients with systemic necrotizing vasculitis. Clin Exp Immunol 101:213–219, 1995
Jung T, Schauer U, Housser C, Neumann C, Rieger C: Detection of intracellular cytokines by flow cytometry. J Immunol Methods 159:197–207, 1993
Qing Y, Pirskanen R, Lefvert AK: Human muscle acetylcholine receptor reactive T and B lymphocytes in the peripheral blood of patients with myasthenia gravis. J Neuroimmunol 42:215–222, 1993
Grunewald J, Andersson R, Rydberg L, Gigliotti D, Schaufelberger C, Hansson G, Wigzell H: CD4+ and CD8+ T cell expansion using selected TCR V and J gene segments at the onset of giant cell arteritis. Arth Rheum 17:1221–1227, 1994
Grunewald J, Tehrani MJ, Andersson R, DerSimonian H, Wigzell H: A persistent monoclonal T cell expansion in the peripheral blood of a normal adult male: A new clinical entity? Clin Exp Immunol 89:279–284, 1992
Grunewald J, Wigzell H: T-cell expansions in healthy individuals. Immunologist 4:99–103, 1996
Fitzgerald JE, Ricalton NS, Meyer AC, West SG, Kaplan H, Behrendt C, Kotzin BL: Analysis of clonal CD8 T cell expansions in normal individuals and patients with rheumatoid arthritis. J Immunol 154:3538–3547, 1995
DeRemee RA: The treatment of Wegener's granulomatosis with trimethoprim/sulfamethoxazole: Illusion or vision? Arth Rheum 31:1068–1072, 1988
Stegeman CA, Tervaert JWC, Jong PED, Kallenberg CGM: Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. N Engl J Med 335:16–20, 1996
Tyndall A, Gratwohl A: Hemopoietic blood and marrow transplants in treatment of severe autoimmune disease. Curr Opin Hematol 4:390–394, 1997
Okumura M, Fujii Y, Inada K, Nakahara K, Matsuda H: Both CD45RA+ and CD45RA− sub populations of CD8+ T cells contain cells with levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells. J Immunol 150:429–437, 1993
Bell EB: Function of CD4 T cell subsets in vivo: Expression of CD45R isoforms. Semin Immunol 4:43–50, 1992
Schlesier M, Kaspar T, Gutfleisch J, Peter HH: Activated CD4+ and CD8+ T cell subsets in Wegener's granulomatosis. Rheumatol Int 14:213–219, 1995
Abo T, Balch CM: A differentiation antigen of human NK and K cells identified by a monoclonal antibody (NHK-1). J Immunol 127:1024–1029, 1981
Lanier LL, Loken MR: Human lymphocyte sub populations identified by using three-color immunofluorescence and flow cytometry analysis: Correlation of Leu-2, Leu-3, Leu-7, Leu-8 and Leu-11 cell surface antigen espression. J Immunol 132:151–156, 1984
Kunemund V, Jungalwala FB, Fischer G, Chou DKH, Keilhauer G, Schachner M: The L2/HNK-1 carbohydrate of neutral cell adhesion molecules is involved in cell interactions. J Cell Biol 106:213–223, 1988
Hoffman S, Edelman GM: A proteoglycan with HNK-1 antigenic determinants is a neuron-associated ligand for cytotactin. Proc Natl Acad Sci USA 84:2523–2527, 1987
Wang ECY, Taylor-Wiedeman J, Perera P, Fisher J, Borysiewicz LK: Subsets of CD8+, CD57+ cells in normal healthy individuals: Correlations with HCMV carrier status, phenotypic and functional analyses. Clin Exp Immunol 94:297–306, 1993
Gratama LW, Kardol M, Naipal AMIH, et al.: The influence of cytomegalovirus carrier status on lymphocyte subsets and natural immunity. Clin Exp Immunol 69:16–24, 1987
Lewis DE, Puck JF, Babcock GF, Rich RR: Disproportionate expansion of a minor T cell subset in patients with lymphadenopathy syndrome and acquired immunodeficiency syndrome. J Infect Dis 151:555–559, 1985
Gupta S: Abnormality of Leu-2+7+ cells in acquired immunodeficiency syndrome (AIDS), AIDS-related complex and asymptomatic homosexuals. J Clin Immunol 6:502–509, 1986
Burns CM, Tsai V, Zvaifler NJ: High percentage of CD8+ Leu 7+ cells in rheumatoid arthritis synovial fluid. Arth Rheum 35:865–873, 1992
Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF: Heterogeneity of large granular lymphocytes proliferations: Delineation of two major subtypes. Blood 68:1142–1153, 1986
Serrano D, Monteiro J, Allen SL, et al.: Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukaemia. J Immunol 158:1482–1489, 1997
Butch AW, Chung GH, Nahm JHH: Cytokine expression by germinal center cells. J Immunol 150:39–47, 1993
Imberti L, Sottini A, Signorini S, Goria R, Primi D: Oligoclonal CD4+CD57+ T-cell expansions contribute to the imbalanced T cell receptor repertoire of rheumatoid arthritis patients. Blood 89:2822–2832, 1997
Chapman A, Stewart SJ, Nepom GT, Green WF, Crowe D, Thomas JW, Miller GG: CD11b+ CD28− CD4+ human T cells Activation requirements and association with HLA-DR alleles. J Immunol 157:4771–4780, 1996
Posnett D, Sinha R, Kabak S, Russo C: Clonal populations of T cells in normal elderly humans: The T cell equivalent to “benign monoclonal gammopathy.” J Exp Med 179:609–618, 1994
Moss P, Gillespie G, Frodsham P, Reyburn H, Bell J: Analysis of clonal expansions within CD4 and CD8 T cells. Immunologist 4:104–105, 1996
Nityanand S, Giscombe R, Srivastaval S, Hjelmström P, Sanjeevi CB, Sinha N, Grunewald J, Lefvert AK: A bias in the αβ T cell receptor variable region gene usage in Takayasu's arteritis. Clin Exp Immunol 107:261–268, 1997
Lúdvíksson BR, Sneller MC, Chua KS, Talar-Williams C, Langford CA, Ehrhardt RO, Fauci AS, Strober W: Active Wegener's granulomatosis is associated with HLA-DR+ CD4+ T cells exhibiting an unbalanced Thl-type T cell cytokine pattern: Reversal with IL-10. J Immunol 160:3602–3609, 1998
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Giscombe, R., Nityanand, S., Lewin, N. et al. Expanded T Cell Populations in Patients with Wegener's Granulomatosis: Characteristics and Correlates with Disease Activity. J Clin Immunol 18, 404–413 (1998). https://doi.org/10.1023/A:1023230722874
Issue Date:
DOI: https://doi.org/10.1023/A:1023230722874