Abstract
In vitro immunoglobulin (Ig) synthesis using a co-culture technique after activation of lymphocytes with pokeweed mitogen, T-cell subsets and interleukin-2 (IL-2) production was studied in 10 children who suffered from IgM mesangial nephropathy (IgMN), 10 children who suffered from minimal change nephrotic syndrome (MCNS) with hypercellularity and 6 children who suffered from MCNS with normal cellularity during the acute nephrotic phase. Reduced in vitro IgG production was found in the presence of OKT8 cells from all groups of patients. However, in vitro IgM production was increased only in OKT8 cells from IgMN and MCNS patients with hypercellularity. In vitro Tac expression on the OKT8 cells, IL-2 production, T-cell subsets including Leu2a+15+ (suppressor T-cells), Leu2a+DR+ (activated suppressor T-cells) and Leu3a+8+ (suppressor T-cell inducer) were all increased in IgMN and MCNS patients with hypercellularity. There was a significant correlation between in vitro IgM production by co-culture technique and IL-2 production. These results strongly suggest the hyperfunction of isotype-specific suppressor T-cells which may affect the switch of IgM B-cells to IgG B-cells in IgMN and MCNS patients with hypercellularity and may be used to explain in part the clinical findings of lower serum IgG and increased IgM in those patients.
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References
Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet I:556–559
Sobel AT, Intrator L, Lague G (1976) Serum immunoglobulins in idiopathic minimal change nephrotic syndrome. N Engl J Med 294:50–51
Fodor P, Sartua MT, Rodriguez E, Gonzalez B, Schlesinger L (1982) T cell dysfunction in minimal change nephrotic syndrome in childhood. Am J Dis Child 136:713–717
White RHR, Glasgow EF, Mills RJ (1970) Clinicopathological study of nephrotic syndrome in childhood. Lancet I:1353–1359
Vaughan III VC, McKay RJ, Behrman RE (1983) Nelson textbook of pediatrics: the nephrotic syndrome, 12th edn. Saunders, Philadelphia, pp 1322–1326
Hsu HC, Chen WY, Lin GJ, Chen L, Kao SL, Huang CC, Lin CY (1984) Clinical and immunopathologic study of mesangial IgM nephropathy: report of 41 cases. Histopathology 8:435–446
Lin CY, Chu CM (1986) Studies of circulating immune complexes and lymphocyte subpopulations in childhood IgM mesangial nephropathy. Nephron 44:198–203
Lin CY (1985) T-cell subsets and response to mitogens in patients with steroid responsive nephrotic syndrome. Chin J Microbiol Immunol 18:13–20
Lin CY (1986) Transient remission after intercurrent measles infection in a patient with hyperIgE syndrome. Pediatr Res 20:685–688
Sternberg JC (1977) A rate nephalometer for measuring specific proteins by immunoprecipitin reactions. Clin Chem 23:1456–1464
Kappler JW, Skidmore B, White J, Marrack P (1981) Antigen-inducible, H-2 restricted, interleukin-2-producing T cell hybridomas. J Exp Med 153:1198–1214
Lin CY, Hwang B (1987) Serial immunological studies in patients with mucocutaneous lymph node syndrome (Kawasaki disease). Ann Allergy59:291–297
Erb P, Vogt P, Meier B, Feldman M (1977) The role of macrophages in the generation of T helper cells. V. Evidence for differential activation of short-lived T1 and long-lived T2 lymphocytes by the macrophage factor GRF and NMF. J Immunol 119:206–209
Keightley RG, Cooper MD, Lawton AR (1976) The T cell dependence of B cell differentiation induced by pokeweed mitogen. J Immunol 117 1538–1544
Hirand T, Kuritani T, Kishimoto T, Yamamura Y (1977) In vitro immune response of human peripheral lymphocytes. I. Mechanism(s) involved in T cell helper functions in the pokeweed mitogen-induced differentiation and proliferation of B cells. J Immunol 119:1235–1241
Lipsky PE, Ginsburg WW, Fickle FD, Ziff M (1978) Enhanced suppressor T cell activity after in vitro incubation. J Immunol 120:902–910
Waldman TA, Broder S, Blaese RM (1974) Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinemia. Lancet II:609–613
Cebra JJ, Komisar JL, Schweitzer PA (1984) CH isotype “switching” during normal B-lymphocyte development. Ann Rev Immunol 2:493–548
Teale JM, Janeway Jr CA (1986) Influence of immunoglobulin-dependent T cells on antibody class switching. J Immunol 137:749–754
Wookland R, Cantor H (1978) Idiotype specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol 8:600–606
Dunn E, Bottomly K (1985) T15 specific helper T cells: analysis of idiotype specificity by competitive inhibition analysis. Eur J Immunol 15:728–732
Reinhere EL, Rubinstein A, Geha RS, Strelkauskas AJ, Rosen FS, Schlossman SF (1979) Abnormalities of immunoregulatory T cells in disorders of immune function. N Engl J Med 301:1018–1022
Hayglass KT, Benacerraf B, Sy MS (1986) The influence of B-cell idiotypes on the repertoire of suppressor T cells. Immunol Today 7:178–183
Kawanishi H, Saltzman L, Strober W (1983) Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissue. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells. J Exp Med 158:649
Dieterle A (1985) Cyclosporin A (CyA) in nephrotic syndrome. Preliminary results of pilot studies. Sandoz, Basle
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Lin, CY., Chen, CH. & Lee, PP. In vitro B-lymphocyte switch disturbance from IgM into IgG in IgM mesangial nephropathy. Pediatr Nephrol 3, 254–258 (1989). https://doi.org/10.1007/BF00858525
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DOI: https://doi.org/10.1007/BF00858525