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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3161-3170
IMMUNOBIOLOGY
Increases in circulating and lymphoid tissue interleukin-10 in
autoimmune lymphoproliferative syndrome are associated with
disease expression
Uri Lopatin,
Xu Yao,
Richard K. Williams,
Jack J. H. Bleesing,
Janet K. Dale,
David Wong,
Julie Teruya-Feldstein,
Scott Fritz,
Matthew R. Morrow,
Ivan Fuss,
Michael C. Sneller,
Mark Raffeld,
Thomas A. Fleisher,
Jennifer M. Puck,
Warren Strober,
Elaine S. Jaffe, and
Stephen E. Straus
From the Laboratory of Clinical Investigation, Clinical
Research Training Program, and Laboratory of Immunoregulation, National
Institute of Allergy and Infectious Diseases, Laboratory of Pathology,
National Cancer Institute, National Human Genome Research Institute,
and Clinical Pathology Department, Warren G. Magnuson Clinical Center,
National Institutes of Health, Bethesda, Maryland; and SAIC, Inc,
Frederick, Maryland.
Autoimmune lymphoproliferative syndrome (ALPS) is an
inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune
manifestations. Some patients with ALPS have relatives with these same
apoptotic defects, however, who are clinically well. This study showed
that the circulating levels of interleukin 10 (IL-10) were
significantly higher (P < .001) in 21 patients with ALPS
than in healthy controls. Moreover, the peripheral blood mononuclear
cells (PBMCs) and lymphoid tissues of these patients with ALPS
contained significantly higher levels of IL-10 messenger RNA (mRNA;
P < .001 and P < .01, respectively). By
fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4 CD8
T-cell population, expansion of which is virtually pathognomonic for
ALPS. Immunohistochemical staining showed intense IL-10 protein signals
in lymph node regions known to contain
CD4CD8 T cells. Nonetheless, in vitro
studies showed no influence of IL-10 on the survival of
CD4CD8 T cells. Overexpression of IL-10 in
patients with inherited apoptotic defects is strongly associated with
the overt manifestations of ALPS.
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