TY - JOUR
T1 - T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated
AU - Willis, Monte S.
AU - Thiele, Geoffrey M.
AU - Tuma, Dean J.
AU - Klassen, Lynell W.
N1 - Funding Information:
This study was supported by the National Institutes of Health (NIAAA R01AA07818, R29AA10435) and the Veterans Affairs Alcohol Research Center. M.W. was the recipient of a MD/PhD Predoctoral Research Fellowship (NIAAA F30AA05487) from the National Institutes of Health. The authors thank Karen Easterling for technical assistance with the flow cytometry experiments.
PY - 2003/10
Y1 - 2003/10
N2 - Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with ∼32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.
AB - Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with ∼32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.
KW - Antigen processing and presentation
KW - Malondialdehyde-acetaldehyde (MAA)
KW - Scavenger receptor
UR - http://www.scopus.com/inward/record.url?scp=0041425158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041425158&partnerID=8YFLogxK
U2 - 10.1016/S1567-5769(03)00136-X
DO - 10.1016/S1567-5769(03)00136-X
M3 - Article
C2 - 12946435
AN - SCOPUS:0041425158
VL - 3
SP - 1381
EP - 1399
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 10-11
ER -