Browsing by Author "Taylor, Justin J."

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    Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum-Specific Atypical Memory B Cells
    (American Association of Immunologists, 2017-06-15) Frosch, Anne E.; Odumade, Oludare A.; Taylor, Justin J.; Ireland, Kathleen; Ayodo, George; Ondigo, Bartholomew; Narum, David L.; Vulule, John; John, Chandy C.; Medicine, School of Medicine
    Human immunodeficiency virus type 1 (HIV-1) infection is associated with B cell activation and exhaustion, and hypergammaglobulinemia. How these changes influence B cell responses to coinfections such as malaria is poorly understood. To address this, we compared B cell phenotypes and Abs specific for the Plasmodium falciparum vaccine candidate apical membrane Ag-1 (AMA1) in HIV-infected and uninfected adults living in Kenya. Surprisingly, HIV-1 infection was not associated with a difference in serum AMA1-specific Ab levels. HIV-infected individuals had a higher proportion of total atypical and total activated memory B cells (MBCs). Using an AMA1 tetramer to detect AMA1-specific B cells, HIV-infected individuals were also shown to have a higher proportion of AMA1-specific atypical MBCs. However, this proportional increase resulted in large part from a loss in the number of naive and resting MBCs rather than an increase in the number of atypical and activated cells. The loss of resting MBCs and naive B cells was mirrored in a population of cells specific for an Ag to which these individuals were unlikely to have been chronically exposed. Together, the data show that changes in P. falciparum Ag-specific B cell subsets in HIV-infected individuals mirror those in the overall B cell population, and suggest that the increased proportion of atypical MBC phenotypes found in HIV-1-infected individuals results from the loss of naive and resting MBCs.
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    Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination
    (American Association for the Advancement of Science, 2022) Tang, Jinyi; Zeng, Cong; Cox, Thomas M.; Li, Chaofan; Son, Young Min; Cheon, In Su; Wu, Yue; Behl, Supriya; Taylor, Justin J.; Chakraborty, Rana; Johnson, Aaron J.; Schiavo, Dante N.; Utz, James P.; Reisenauer, Janani S.; Midthun, David E.; Mullon, John J.; Edell, Eric S.; Alameh, Mohamad G.; Borish, Larry; Teague, William G.; Kaplan, Mark H.; Weissman, Drew; Kern, Ryan; Hu, Haitao; Vassallo, Robert; Liu, Shan-Lu; Sun, Jie; Microbiology and Immunology, School of Medicine
    SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.
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    Tissue-resident CD4+ T helper cells assist the development of protective respiratory B and CD8+ T cell memory responses
    (American Association for the Advancement of Science, 2021) Son, Young Min; Cheon, In Su; Wu, Yue; Li, Chaofan; Wang, Zheng; Gao, Xiaochen; Chen, Yao; Takahashi, Yoshimasa; Fu, Yang-Xin; Dent, Alexander L.; Kaplan, Mark H.; Taylor, Justin J.; Cui, Weiguo; Sun, Jie; Microbiology and Immunology, School of Medicine
    Much remains unknown about the roles of CD4+ T helper cells in shaping localized memory B cell and CD8+ T cell immunity in the mucosal tissues. Here, we report that lung T helper cells provide local assistance for the optimal development of tissue-resident memory B and CD8+ T cells after the resolution of primary influenza virus infection. We have identified a population of T cells in the lung that exhibit characteristics of both follicular T helper and TRM cells, and we have termed these cells as resident helper T (TRH) cells. Optimal TRH cell formation was dependent on transcription factors involved in T follicular helper and resident memory T cell development including BCL6 and Bhlhe40. We show that TRH cells deliver local help to CD8+ T cells through IL-21-dependent mechanisms. Our data have uncovered the presence of a tissue-resident helper T cell population in the lung that plays a critical role in promoting the development of protective B cell and CD8+ T cell responses.