Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0208100 on April 24, 2008

Published online before print April 24, 2008
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(Journal of Leukocyte Biology. 2008;84:170-181.)
© 2008 by Society for Leukocyte Biology

The acute phase protein haptoglobin regulates host immunity

Kristin M. Huntoon*,1, Yanping Wang*,1,2, Cheryl A. Eppolito{dagger}, Karen W. Barbour{ddagger}, Franklin G. Berger{ddagger}, Protul A. Shrikant{dagger} and Heinz Baumann*,3

Departments of
* Molecular and Cellular Biology and
{dagger} Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA; and
{ddagger} Department of Biology, University of South Carolina, Columbia, South Carolina, USA

3Correspondence: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. E-mail: heinz.baumann{at}roswellpark.org

The contribution of acute phase plasma proteins to host immune responses remains poorly characterized. To better understand the role of the acute phase reactant and major hemoglobin-binding protein haptoglobin (Hp) on the function of immune cells, we generated Hp-deficient C57BL/6J mice. These mice exhibit stunted development of lymphoid organs associated with lower counts of mature T and B cells in the blood and secondary lymphoid compartments. Moreover, these mice show markedly reduced adaptive immune responses as represented by reduced accumulation of IgG antibody after immunization with adjuvant and nominal antigen, abrogation of Th1-dominated delayed-type hypersensitivity reaction, loss of mitogenic responses mounted by T cells, and reduced T cell responses conveyed by APCs. Collectively, these defects are in agreement with the observations that Hp-deficient mice are not capable of generating a recall response or deterring a Salmonella infection as well as failing to generate tumor antigen-specific responses. The administration of Hp to lymphocytes in tissue culture partially ameliorates these functional defects, lending further support to our contention that the acute phase response protein Hp has the ability to regulate immune cell responses and host immunity. The phenotype of Hp-deficient mice suggests a major regulatory activity for Hp in supporting proliferation and functional differentiation of B and T cells as part of homeostasis and in response to antigen stimulation.

Key Words: T cell • dendritic cell • humoral immune response






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