Browsing by Author "Cautivo, Kelly M."

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    Efficient Lung Recruitment of Respiratory Syncytial Virus-Specific Th1 Cells Induced by Recombinant Bacillus Calmette-Guerin Promotes Virus Clearance and Protects from Infection
    (AMER ASSOC IMMUNOLOGISTS, 2010) Cautivo, Kelly M.; Bueno, Susan M.; Cortes, Claudia M.; Wozniak, Aniela; Riedel, Claudia A.; Kalergis, Alexis M.
    Infection by the respiratory syncytial virus (RSV) can cause extensive inflammation and lung damage in susceptible hosts due to a Th2-biased immune response. Such a deleterious inflammatory response can be enhanced by immunization with formalin- or UV-inactivated RSV, as well as with vaccinia virus expressing the RSV-G protein. Recently, we have shown that vaccination with rBCG-expressing RSV Ags can prevent the disease in the mouse. To further understand the immunological mechanisms responsible for protection against RSV, we have characterized the T cell populations contributing to virus clearance in mice immunized with this BCG-based vaccine. We found that both CD4(+) and CD8(+) T cells were recruited significantly earlier to the lungs of infected mice that were previously vaccinated. Furthermore, we observed that simultaneous adoptive transfer of CD8(+) and CD4(+) RSV-specific T cells from vaccinated mice was required to confer protection against virus infection in naive recipients. In addition, CD4(+) T cells induced by vaccination released IFN-gamma after RSV challenge, indicating that protection is mediated by a Th1 immune response. These data suggest that vaccination with rBCG-expressing RSV Ags can induce a specific effector/memory Th1 immune response consisting on CD4(+) and CD8(+) T cells, both necessary for a fully protective response against RSV. These results support the notion that an effective induction of Th1 T cell immunity against RSV during childhood could counteract the unbalanced Th2-like immune response triggered by the natural RSV infection. The Journal of Immunology, 2010, 185: 7633-7645.
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    FcγRIIb and BAFF Differentially Regulate Peritoneal B1 Cell Survival
    (2012) Amezcua Vesely, Maria C.; Schwartz, Marc; Bermejo, Daniela A.; Montes, Carolina L.; Cautivo, Kelly M.; Kalergis, Alexis M.; Rawlings, David J.; Acosta-Rodriguez, Eva V.; Gruppi, Adriana
    B1 cells produce most natural Abs in unimmunized mice and play a key role in the response to thymus-independent Ags and microbial infection. Enlargement of B1 cell number in mice is often associated with autoimmunity. However, the factors that control peripheral B1 cell survival remain poorly characterized. Mice lacking the inhibitory receptor Fe gamma RIIb exhibit a massive expansion in peritoneal B1 cells, implicating this receptor in B1 cell homeostasis. In this study, we show that peritoneal B1 cells express the highest levels of Fc gamma RIIb among B cell subsets and are highly susceptible to Fe gamma RIIb-mediated apoptosis. B1 cells upregulate Fc gamma RIIb in response to innate signals, including CpG, and the B cell homeostatic cytokine BAFF efficiently protects activated B1 cells from Fc gamma IIb-mediated apoptosis via receptor downregulation. BAFF-transgenic mice manifest an expansion of peritoneal B1 cells that express lower levels of Fc gamma RIIb and exhibit reduced susceptibility to apoptosis. Whereas both peritoneal B1 cells from wild-type and BAFF-transgenic mice immunized with CpG exhibit an increase in Fc gamma RIIb levels, this change is blunted in BAFF-transgenic animals. Our combined results demonstrate that Fc gamma RIIb controls peritoneal B1 cell survival and this program can be modulated. by the BAFF signaling axis. The Journal of Immunology, 2012, 188: 4792-4800.