Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 181, Issue 5, Pages 1725-1734Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2012.07.034
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Funding
- Connecticut Institute for Clinical and Translational Science Clinical and Translational Scholars K12 Award
- Lea's Foundation for Leukemia Research, Inc.
- National Institute of Allergy and Infectious Diseases [RO1 AI04357-11]
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Although functional asplenia from infarctions may be a major contributor to increased infectious mortality in sickle-cell disease (SCD), this relationship has not been fully defined. We used the transgenic Berkeley SCD mouse to define blood and splenic immunophenotypic differences in this model compared with C57BL/6 and hemizygous controls. In the serum of SCD mice, we found increased IgG2a and suppressed IgM, IgG2b, and IgA levels. Serum IL-6 levels in SCD mice were elevated, whereas IL-1 alpha, CXCL10, and CCL5 levels were decreased. The blood of SCD mice had higher white blood cell counts, with an increased percentage of lymphocytes and decreases in other leukocytes. Immunophenotyping of lymphocytes revealed higher percentages of CD8(+) and T-regulatory cells and lower percentages of B cells. SCD mouse spleens exhibited histological disorganization, with reduction of defined lymphoid follicles and expansion of red pulp, a greater than fourfold increase in splenic mononuclear cells, marked expansion of the nucleated red blood cell fraction, and B-cell and CD8+ T-cell lymphopenia. Within the splenic B-cell population, there was a significant decrease in B-la B cells, with a corresponding decrease in IgA secreting plasma cells in the gut. Confocal microscopy of spleens demonstrated complete disruption of the normal lymphofollicular structure in the white pulp of SCD mice without distinct B, T, and marginal zones. Our findings suggest that altered SCD splenic morphological characteristics result in an impaired systemic immune response. (Am J Pathol 2012, 181: 1725-1734; http://dx.doi.org/10.1016/j.ajpath.2012.07.034)
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