TY - JOUR
T1 - B lymphocytes are required during the early priming of CD4+ T cells for clearance of pneumocystis infection in mice
AU - Opata, Michael M.
AU - Hollifield, Melissa L.
AU - Lund, Frances E.
AU - Randall, Troy D.
AU - Dunn, Robert
AU - Garvy, Beth A.
AU - Feola, David J.
N1 - Publisher Copyright:
© 2015 by The American Association of Immunologists, Inc.
PY - 2015/7/15
Y1 - 2015/7/15
N2 - B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4+ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell-deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4+ T cells requires B cells during the first 2-3 d of infection and that this was independent of the production of Ab. T cells that were removed from Pneumocystis-infected mice during the priming phase were fully functional and able to clear Pneumocystis infection upon adoptive transfer into Rag1-/- hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of Ag presentation and activation signals to become fully functional in this model of Pneumocystis infection.
AB - B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4+ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell-deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4+ T cells requires B cells during the first 2-3 d of infection and that this was independent of the production of Ab. T cells that were removed from Pneumocystis-infected mice during the priming phase were fully functional and able to clear Pneumocystis infection upon adoptive transfer into Rag1-/- hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of Ag presentation and activation signals to become fully functional in this model of Pneumocystis infection.
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U2 - 10.4049/jimmunol.1500112
DO - 10.4049/jimmunol.1500112
M3 - Article
C2 - 26041535
AN - SCOPUS:84936792334
VL - 195
SP - 611
EP - 620
IS - 2
ER -