Immune Response to Chemically Modified Flagellin

Abstract

Recent studies in this laboratory have indicated that humoral and cell-mediated immunity may be intimately related (1-3). Using a series of acetoacetylated derivatives of flagellin, it was observed that increasing acetoacetylation steadily destroyed the ability of flagellin to initiate antibody formation but enhanced the capacity of the molecule to induce flagellin-specific delayed-type hypersensitivity and antibody tolerance. Thus, in this system antibody tolerance in adult rats was accompanied by enhanced cell-mediated immunity. If this relationship represents a general phenomenon, then it would be predicted that all states of antibody tolerance in adult animals should be accompanied by enhanced cell-mediated immunity. Using bacterial flagellin as the antigen, studies were initiated to test this prediction. I t has been previously reported that antibody tolerance to flagellin can be induced in adult rats by multiple injections of a cyanogen bromide (CNBr) digest of flagellin at two widely spaced dose levels (4). This phenomenon is called high and low zone antibody tolerance (5). Intermediate doses of the C N B r digest resulted in very high antibody titers rather than in antibody tolerance. D a t a presented in this paper reveal that, as predicted, both high and low zone antibody tolerance to flagellin were associated with heightened levels of delayed-type hypersensitivity. Furthermore, when enhancement of the antibody response occurred, suppression of delayed-type hypersensitivity was observed. Thus, an inverse relationship appears to exist between humoral and cell-mediated immunity. However, this relationship is not invariably true as rats from another strain exhibited only a partial inverse relationship. In addition, it was confirmed (3) that administration of antigen to neonatal rats induced tolerance at the level of both humoral and cell-mediated immunity. Materials and Methods Animals.---Outbred

Human T‐ and B‐Cell Reactivity to the 16 kDa α‐Crystallin Protein of Mycobacterium tuberculosis

“…The generally perceived reciprocal relationship between antibody production and 'cell-mediated' immunity was first described by Parish & Liew [15]. The negative correlation between antibody production and cell proliferation has previously been observed in human tuberculosis [14,[16][17][18].…”

Characterization of CD4+ T Cell Responses During Natural Infection with Salmonella typhimurium

“…Flagellar proteins from Salmonella have long been the subject of study by immunologists due to their immunogenic properties and the capacity for polymerization and depolymerization of the filament (32). In addition, a recent report has described the production of TNF-␣ from a human promonocytic cell line in response to FliC (33), suggesting that there may be an inherent adjuvant effect attributable to FliC itself.…”

Bacterial Flagellin Is an Effective Adjuvant for CD4+ T Cells In Vivo

“…Bacterial flagellin has long been studied as a useful model Ag (19,20) and was recently found to be a target of CD4 T cells during murine Salmonella typhimurium infection (21)(22)(23). In addition to being a target of the adaptive immune system, bacterial flagellin can directly activate innate immune responses in monocytes (24 -26) and epithelial cells (27,28).…”