Alum adjuvant boosts

Alum adjuvant boosts - Published March 24, 2008 ARTICLE...

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The Journal of Experimental Medicine ARTICLE JEM © The Rockefeller University Press $30.00 Vol. 205, No. 4, April 14, 2008 869-882 869 10.1084/jem.20071087 Aluminum-containing adjuvants have histori- cally served as immunopotentiators in vaccines and continue to be the most widely used clini- cal adjuvants ( 1 ). Despite the fact that millions of doses of aluminum-containing adjuvants have been given to healthy populations, it is surprising that there is no consensus regarding the mechanisms by which they potentiate the immune system ( 2 – 7 ). The following three potential mechanisms are frequently cited to explain how these adjuvants increase humoral immunity, although scarce experimental evi- dence is publicly available: (a) the formation of a depot by which the Ag is slowly released to enhance the antibody production; (b) the in- duction of inF ammation, thus recruiting and activating APCs that capture the Ag ( 8 ); and (c) the conversion of soluble Ag into a particulate form so that it is phagocytosed by APCs such as macrophages, DCs, and B cells. It is common knowledge that aluminum-containing adju- vants (alum) predominantly induce humoral immunity, an observation that is further sup- ported by the recent discovery that alum induces B cell priming and Ca 2+ mobilization via a splenic Gr-1 + myeloid IL-4 – producing cell type ( 5 ). Classical cell-mediated immunity measured by DTH responses and induction of CD8 + CTL responses to a range of polypeptide and protein Ags is poorly induced by alum, caused by a lack of cross-priming ( 9, 10, 1 ). However, pro- liferative responses of CD4 + T cells, as well as Th2 cytokine production, have been found to be enhanced in several murine and human stud- ies, suggesting that alum boosts humoral immu- nity by providing Th2 cell help to follicular B cells ( 11, 8, 2 ). DCs are seen as nature ’ s adjuvant and have the potential to recognize foreign Ag, process it into small peptides for presentation onto MHC molecules to the TCR, and provide the essen- tial costimulatory molecules for activation of naive CD4 + and CD8 + T cells ( 12 ). DCs have an immature phenotype in peripheral tissues, specialized for Ag uptake, but upon recognition of exogenous or endogenous “ danger signals ” like uric acid or extracellular ATP, they migrate to the LN T cell paracortex, where they arrive CORRESPONDENCE Bart N. Lambrecht: ± Abbreviations used: Ag, antigen; Alum, aluminum hydroxide; CLN, cervical LN; DLN, drain- ing LN; DT, diphteria toxin; DTR, DT receptor; ILN, in- guinal LN; i.t., intratracheal; MLN, mediastinal LN; Tg, transgenic. M. Kool, T. Soulli é , H. Hammad, and B.N. Lambrecht con- tributed equally to this paper. The online version of this article contains supplemental material. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inf ammatory dendritic cells Mirjam Kool, 1 Thomas Soulli é , 1 Menno van Nimwegen, 1 Monique A.M. Willart, 1,2 Femke Muskens, 1 Ste± en Jung, 3 Henk C. Hoogsteden, 1 Hamida Hammad, 1,2 and Bart N. Lambrecht 1,2 1
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Alum adjuvant boosts - Published March 24, 2008 ARTICLE...

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