First published May 1, 2009 - More info
Chronic infections are associated with progressively declining T cell function. Infections with helminth parasites, such as Schistosoma mansoni, are often chronic and characterized by the development of strong Th2 responses that peak during the acute stage of infection and then decline despite ongoing infection; this minimizes Th2-dependent immunopathology during the chronic stage of infection. We sought to understand the basis for the decline in Th2 responses in chronic schistosomiasis. Using IL-4 reporter mice (mice that express EGFP as a reporter for Il4 gene expression) to identify Th2 cells, we found that Th2 cell numbers plateaued during acute infection and remained constant thereafter. However, the percentages of Th2 cells proliferating during late infection were strikingly lower than those during acute infection. Th2 cell hyporesponsiveness was evident within 10 d of initiation of the Th2 response and became progressively ingrained thereafter, in response to repeated Ag stimulation. Gene expression analyses implicated the E3-ubiquitin ligase gene related to anergy in lymphocytes (GRAIL) in the hyporesponsive state. Consistent with this, suppression of GRAIL expression using retrovirally delivered siRNA prevented the development of hyporesponsiveness induced by repeated Ag stimulation in vitro or in vivo. Together, these data indicate that the decline in Th2 cell responsiveness during chronic schistosomiasis is the net result of the upregulation of GRAIL expression in response to repeated Ag stimulation.
Justin J. Taylor, Connie M. Krawczyk, Markus Mohrs, Edward J. Pearce
Original citation: J. Clin. Invest.119:1019–1028 (2009). doi:10.1172/JCI36534.
Citation for this corrigendum: J. Clin. Invest.119:1396 (2009). doi:10.1172/JCI36534E1.
During the preparation of the manuscript, the mice in Figure 2 were incorrectly identified as having been infected with S. mansoni. The correct legend for Figure 2A appears below.
(A) Mice received 1 or more egg injections. Repeat egg injections were 5 d apart, such that mice for the 20-d time point had received 4 injections prior to sacrifice. At 5, 10, 15, and 20 d after the first immunization, CD4+ T cells from draining popliteal LNs were analyzed ex vivo for the expression of IL-4/GFP by flow cytometry. Numbers within plots indicate mean ± SD percent of CD4+ cells that were IL-4/GFP+ (3 mice per group).
The JCI regrets the error.