Bacterial Lipoproteins Differentially Regulate Human Primary and Memory CD4+ T and B Cell Responses to Pneumococcal Protein Antigens through Toll‐Like Receptor 2

Abstract

Bacterial lipoproteins (BLPs) are expressed across a range of bacteria and are able to activate Toll-like receptor 2 (TLR-2). BLPs enhance immune responses in naive individuals and have therefore been tested as candidate vaccine adjuvants. It is not known whether BLPs affect any preexisting immunity (eg, memory cell response in primed individuals). Colonization with pneumococcus (PNC), which primes for memory cell response, is common in young children. We studied effects of BLPs on memory and primary B and CD4+ T cell responses to pneumococcal proteins using adenoidal cells from children. Although BLPs enhanced the primary antibody responses seen in some children with no detectable nasal PNC, BLPs unexpectedly reduced the memory antibody responses in children with positive nasal culture results. Likewise, BLPs augmented the naive but inhibited the memory antigen-driven CD4+ T cell response. The downregulation of the memory responses was associated with increases in interleukin 10 and inducible costimulatory molecule expression, as well as a decrease in CD28 expression in memory CD4+ T cells; all were blocked by anti-TLR2 and anti-B7h antibodies. Augmentation of naive CD4+ T cell proliferation was blocked by anti-B7.2. Differential regulation of primary and memory responses by BLPs through TLR2 may have important implications for therapeutic and vaccination strategies against bacterial infection.