Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release.
T helper cell type 1 (Th1) and type 2 (Th2) immune responses are characterized by a different pattern of cytokine expression following T-cell activation. Alterations of the ratio of Th1 to Th2 cells are important determinants of susceptibility to viral and parasitic infections, allergies, anti-tumour responses, and autoimmunity. In this work we bring new evidence for an effect of haptoglobin (Hp), a positive acute-phase protein, on T-lymphocyte functions. We show that Hp specifically interacts with both resting and activated CD4+ and CD8+ T cells. This specific binding results in a strong suppression of induced T-cell proliferation. In addition, Hp exhibits a strong in vitro inhibitory effect on Th2 cytokine release, while the production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) is only slightly inhibited at high Hp doses. As a result, the presence of Hp promotes Th1 activation over Th2 activation in vivo as evidenced in Hp-deficient mice. Anti-CD3 monoclonal antibody injection indeed resulted in predominant IL-4 production in Hp-/- mice, in contrast to predominant IFN-gamma production in Hp+/+ mice. We conclude that Hp plays a modulating role on the Th1/Th2 balance by promoting a dominant Th1 cellular response. This points to a role of acute-phase proteins in balancing immune responses.
Arredouani
M
M
Laboratory for Experimental Immunology, Gasthuisberg University Hospital, Leuven, Belgium.
Matthijs
P
P
Van Hoeyveld
E
E
Kasran
A
A
Baumann
H
H
Ceuppens
J L
JL
Stevens
E
E
D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D006242:Haptoglobins / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010835:Phytohemagglutinins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D016207:Cytokines; D006242:Haptoglobins; D010835:Phytohemagglutinins