Clinical Investigation

Kidney International (1984) 25, 557–564; doi:10.1038/ki.1984.54

T cell subset modulation of immunoglobulin production in IgA nephropathy and membranous glomerulonephritis

Eugène Rothschild1 and Lucienne Chatenoud1

1Institut National de la Santé et de la Recherche Medicale, Unité 25, Necker Hôpital, Paris, France

Correspondence: Dr E Rothschild, INSERM Unité 25, Hôpital Necker, 151, rue de Sèvres, 74015 Paris, France

Received 8 December 1982; Revised 17 August 1983.

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Abstract

T cell subset modulation of immunoglobulin production in IgA nephropathy and membranous glomerulonephritis. Monoclonal antibodies directed against T cell subset antigens have been used to deplete peripheral blood human mononuclear cells from helper (OKT4+) and suppressor/cytotoxic (OKT8+) cells. Unfractionated cells and depleted cells were assayed for their capacity to modulate pokeweed mitogen (PWM)-driven IgG, IgA, and IgM production by autologous B lymphocytes. Immunoglobulin production in the presence of these various cell preparations paralleled the OKT4+/OKT8+ ratio defining the population. Importantly, there was no clear relationship between the level of PWM-driven Ig production by unfractionated cells and their initial relative content in OKT4+ and OKT8+ cells. Patients with IgA nephropathy and membranous glomerulonephritis showed a statistically significant increase of OKT4+/OKT8+ ratio, suggestive of suppressor T cell deficiency. There was no increase in IgA production in patients with IgA nephropathy, even in those showing high serum IgA level. A special feature found in patients with IgA nephropathy, irrespective of OKT4+/OKT8+ ratio in unfractionated cells, was a particularly intense enhancement of IgA production after OKT8+ cell depletion in some of the patients, contrasting with a particularly low effect of such depletion on the synthesis of all Ig classes in other patients. In patients with membranous glomerulonephritis there was no obvious abnormality in the modulation of Ig production by T cell subsets, with the exception of a weak suppressor activity with respect only to IgM production in a significant number of patients.

Modulation par les sous-populations lymphocytaires T de la production d'immunoglobulines dans les glomérulonéphrites à dépôts intercapillaires d'IgA et extra-membraneuses. Des anticorps monoclonaux reconnaissant les antigènes des sous-populations lymphocytaires T ont servi à appauvrir des préparations de cellules mononucléées du sang circulant en lymphocytes inducteurs (OKT4+) et suppresseurs/cytotoxiques (OKT8+). C'est la capacité de ces diverses préparations cellulaires, non fractionnées et purifiées, à moduler la production d'IgG, d'IgA, et d'IgM par les cellules B autologues en réponse au pokeweed-mitogène (PWM), qui a été étudiée. La production d'immunoglobulines en présence de ces diverses préparations cellulaires est parallèle au rapport OKT4+/OKT8+ définissant la population cellulaire en cause. Il faut noter l'absence de corrélation nette entre le taux d'immunoglobulines produites en réponse au PWM par les cellules non fractionnées et leur contenu initial en lymphocytes OKT4+ et OKT8+. Dans les glomérulonéphrites à dépôts intercapillaires d'IgA et extra-membraneuses, le rapport OKT4+/OKT8+ est élevé de façon statistiquement significative, ce qui suggère un déficit numérique des cellules T suppressives. La production d'IgA n'est pas accrue dans les glomérulonéphrites à dépôts d'IgA, même chez les malades ayant un taux sérique d'IgA élevé. De façon propre aux glomérulonéphrites à dépôts d'IgA, indépendamment du rapport OKT4+/OKT8+ initial des cellules non fractionnées, l'appauvrissement en lymphocytes OKT8+ est suivi chez une fraction de malades par une exacerbation particulièrement intense de la production d'IgA, tandis que chez les autres, cette purification n'a qu'un très faible effet sur la synthèse des trois classes d'immunoglobulines. Dans les glomérulonéphrites extramembraneuses, on ne constate pas d'anomalie grossière de la modulation par les souspopulations T de la production d'immunoglobulines hormis la faible activité suppressive, à l'égard de la production d'IgM uniquement, présente chez une partie des patients.

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