TRACP Influences Th1 pathways by affecting dendritic cell function.
TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo. We postulate that TRACP has an important role in the presentation of antigens to T cells.


BACKGROUND
TRACP is highly expressed by osteoclasts, activated macrophages, and dendritic cells (DCs). Knockout mice lacking TRACP have an intrinsic defect in osteoclastic resorption and macrophages that display abnormal immunomodulatory responses and cytokine secretion profiles. Our aim in this study was to investigate the significance of TRACP in the inductive phase of the immune response by examining dendritic cells from TRACP(-/-) mice.


METHODS
Maturational state and function of leukocyte subsets in mice was assessed by flow cytometry. The ability of the immune system to respond to nonspecific activation and to specific antigen was assessed by delayed type hypersensitivity and the presence of isotype-specific serum antibody in vivo and T-cell proliferation and cytokine production in vitro.


RESULTS
The ability of lipopolysaccharide (LPS) to upregulate MHC II and CD80 in DCs from TRACP(-/-) mice was reduced compared with wildtype mice, although production of IL-10 by DCs from TRACP-deficient animals was increased. T- and B-cell responses not involving antigen presentation (anti-CD3, TNP-ficoll) were normal in TRACP(-/-) mice, but responses to T-dependent antigens were impaired. Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice. In response to ovalbumin, but not anti-CD3, T cells from TRACP(-/-) mice produced less interferon-gamma (IFN-gamma), but there was no difference in IL-4 production: TRACP(-/-) mice also produced less ovalbumin (OVA)-specific IgG2a after immunization.


CONCLUSIONS
The finding that DCs from TRACP(-/-) mice have impaired maturation and defective Th1 responses shows that TRACP is important for polarizing responses in naïve T cells to antigen-presented dendritic cells.
Esfandiari
Ehsanollah
E
School of Clinical Veterinary Science, University of Bristol, Bristol, United Kingdom.
Bailey
Michael
M
Stokes
Christopher R
CR
Cox
Timothy M
TM
Evans
Martin J
MJ
Hayman
Alison R
AR
D000135:Acid Phosphatase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology*; D004423:Ear / Q000254:growth & development; D000939:Epitopes; D005260:Female; D006968:Hypersensitivity, Delayed; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010853:Picryl Chloride / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D000071681:Tartrate-Resistant Acid Phosphatase; D018417:Th1 Cells / Q000502:physiology*
D000939:Epitopes; D007527:Isoenzymes; D016753:Interleukin-10; D018664:Interleukin-12; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D010853:Picryl Chloride