IL-4 Synergizes with IL-10 and Anti-CD40 MoAbs to Induce B-Cell Differentiation in Patients with Common Variable Immunodeficiency.

Autor: Punnonen, J., Kainulainen, L., Ruuskanen, O., Nikoskelainen, J., Arvilommi, H.
Předmět:
Zdroj: Scandinavian Journal of Immunology; Feb1997, Vol. 45 Issue 2, p203-212, 10p, 3 Charts, 2 Graphs
Abstrakt: In the present study the phenotype and function of lymphocytes from patients with common variable immunodeficiency (CVI) were studied. Five out of 12 patients had abnormally low proportion of CD4+ T cells, but PBMC of these patients were capable of proliferating in response to polyclonal T-cell mitogens or PPD antigen. The phenotype of patients' B cells, as determined by expression of CD10, CD19 and CD34, was comparable to that of healthy controls. IL-4 and anti-CD40 MoAbs induced moderate B-cell differentiation in PBMC derived from patients with CVI, but the frequencies of Ig-secreting cells were generally at levels spontaneously observed in healthy controls. IL-10 was completely ineffective in inducing IgG-secreting cells in cultures of PBMC derived from patients with CVI even in the presence of anti CD40 MoAbs, whereas high frequencies of Ig-secreting cells were induced under similar condition in cultures of PBMC derived from healthy controls. Importantly, when IL-4 was added to cultures stimulated with anti-CD40 MoAbs and IL-10. a very strong synergistic effect on the numbers of Ig-secreting cells and the levels of Ig secretion was observed in PBMC from both patients and controls. Moreover, the frequencies of Ig-secreting cells after activation with anti-CD40 MoAbs, IL-4 plus IL-10 in PBMC from some patients were comparable to those observed in PBMC from healthy controls. Taken together, these results indicate that B cells from patients with CVI have impaired capacity to differentiate into Ig-secreting cells in response to IL- 10 and anti-CD40 MoAbs, and that this unresponsiveness can be restored by exogenous IL-4 in a proportion of the patients. [ABSTRACT FROM AUTHOR]
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