scholarly journals LAPCs promote follicular helper T cell differentiation of Ag-primed CD4+ T cells during respiratory virus infection

2012 ◽  
Vol 209 (10) ◽  
pp. 1853-1867 ◽  
Author(s):  
Jae-Kwang Yoo ◽  
Eleanor N. Fish ◽  
Thomas J. Braciale
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Influenza A ◽  
Respiratory Virus ◽  
Cell Development ◽  
Virus Infections ◽  
Humoral Immune ◽  
Follicular Helper ◽  
Primary Antibody Response ◽  
Follicular Helper T Cell

The humoral immune response to most respiratory virus infections plays a prominent role in virus clearance and is essential for resistance to reinfection. T follicular helper (Tfh) cells are believed to support the development both of a potent primary antibody response and of the germinal center response critical for memory B cell development. Using a model of primary murine influenza A virus (IAV) infection, we demonstrate that a novel late activator antigen-presenting cell (LAPC) promotes the Tfh response in the draining lymph nodes (dLNs) of the IAV-infected lungs. LAPCs migrate from the infected lungs to the dLN “late,” i.e., 6 d after infection, which is concomitant with Tfh differentiation. LAPC migration is CXCR3-dependent, and LAPC triggering of Tfh cell development requires ICOS–ICOSL–dependent signaling. LAPCs appear to play a pivotal role in driving Tfh differentiation of Ag-primed CD4+ T cells and antiviral antibody responses.

scholarly journals Functional STAT3 deficiency compromises the generation of human T follicular helper cells

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 3997-4008 ◽  
Author(s):  
Cindy S. Ma ◽  
Danielle T. Avery ◽  
Anna Chan ◽  
Marcel Batten ◽  
Jacinta Bustamante ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Cell Development ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Helper Activity ◽  
And Function

Abstract T follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify the molecular requirements for Tfh cell development and function. We previously found that IL-12 mediates the differentiation of human CD4+ T cells to the Tfh lineage, because IL-12 induces naive human CD4+ T cells to acquire expression of IL-21, BCL6, ICOS, and CXCR5, which typify Tfh cells. We have now examined CD4+ T cells from patients deficient in IL-12Rβ1, TYK2, STAT1, and STAT3 to further explore the pathways involved in human Tfh cell differentiation. Although STAT1 was dispensable, mutations in IL12RB1, TYK2, or STAT3 compromised IL-12–induced expression of IL-21 by human CD4+ T cells. Defective expression of IL-21 by STAT3-deficient CD4+ T cells resulted in diminished B-cell helper activity in vitro. Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell generation in vivo, evidenced by decreased circulating CD4+CXCR5+ T cells. These results highlight the nonredundant role of STAT3 in human Tfh cell differentiation and suggest that defective Tfh cell development and/or function contributes to the humoral defects observed in STAT3-deficient patients.

scholarly journals Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 69
Author(s):  
Evan J. Anderson ◽  
Lilin Lai ◽  
Jens Wrammert ◽  
Sarah Kabbani ◽  
Yongxian Xu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cd4 T Cells ◽  
Cellular Responses ◽  
Memory B Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Free Jet ◽  
Follicular Helper ◽  
Follicular Helper T Cell

Background: Vaccinia is known to induce antibody and cellular responses. Plasmablast, circulating follicular helper T (cTFH) cells, cytokine-expressing CD4 T cells, and memory B cells were compared between subcutaneous (SC) and needle-free jet injection (JI) recipients of non-replicating modified vaccinia Ankara (MVA) vaccine. Methods: Vaccinia-naïve adults received MVA SC or by JI on Days 1 and 29. Vaccinia-specific antibodies were quantified by plaque reduction neutralization test (PRNT) and enzyme-linked immunosorbent assay. Plasmablast, cTFH, and cytokine-expressing CD4 T cells were assessed on Days 1, 8, 15, 29, 36, 43 (cTFH and CD4+ only) and 57. Memory B cells were measured on Days 1 and 57. Results: Of the 36 enrolled subjects, only 22 received both vaccinations and had evaluable specimens after the second vaccine. Plasmablasts peaked one week after each vaccine. Day 15 plasmablasts correlated with peak PRNT titers. cTFH peaked on Days 8 and 36 and correlated with Day 36 plasmablasts. CD4+ peaked at Day 29 and one-third produced ≥2 cytokines. Day 57 memory B cells ranged from 0.1% to 0.17% of IgG-secreting B cells. Conclusions: This study provides insights into the cellular responses to non-replicating MVA, currently used as a vector for a variety of novel vaccines.

scholarly journals Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity

2021 ◽  
Vol 17 (2) ◽  
pp. e1009288
Author(s):  
Fionna A. Surette ◽  
Jenna J. Guthmiller ◽  
Lei Li ◽  
Alexandria J. Sturtz ◽  
Rahul Vijay ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Humoral Immunity ◽  
Cd4 T Cells ◽  
Virus Infections ◽  
Follicular Helper ◽  
B Cell Survival ◽  
Cellular Source ◽  
Cell Expression

Immunity against malaria depends on germinal center (GC)-derived antibody responses that are orchestrated by T follicular helper (TFH) cells. Emerging data show that the regulatory cytokine IL-10 plays an essential role in promoting GC B cell responses during both experimental malaria and virus infections. Here we investigated the cellular source and temporal role of IL-10, and whether IL-10 additionally signals to CD4 T-cells to support anti-Plasmodium humoral immunity. Distinct from reports of virus infection, we found that IL-10 was expressed by conventional, Foxp3-negative effector CD4 T cells and functioned in a B cell-intrinsic manner only during the first 96 hours of Plasmodium infection to support humoral immunity. The critical functions of IL-10 manifested only before the orchestration of GC responses and were primarily localized outside of B cell follicles. Mechanistically, our studies showed that the rapid and transient provision of IL-10 promoted B cell expression of anti-apoptotic factors, MHC class II, CD83, and cell-cell adhesion proteins that are essential for B cell survival and interaction with CD4 T cells. Together, our data reveal temporal features and mechanisms by which IL-10 critically supports humoral immunity during blood-stage Plasmodium infection, information that may be useful for developing new strategies designed to lessen the burden of malaria.

scholarly journals Protection from Respiratory Virus Infections Can Be Mediated by Antigen-Specific Cd4+ T Cells That Persist in the Lungs

2001 ◽  
Vol 193 (8) ◽  
pp. 981-986 ◽  
Author(s):  
Robert J. Hogan ◽  
Weimin Zhong ◽  
Edward J. Usherwood ◽  
Tres Cookenham ◽  
Alan D. Roberts ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Cellular Immunity ◽  
Cd4 T Cells ◽  
Respiratory Virus ◽  
Critical Role ◽  
Lymphoid Tissues ◽  
Virus Infections ◽  
Respiratory Virus Infections ◽  
Memory Cd4 T Cells

Although CD4+ T cells have been shown to mediate protective cellular immunity against respiratory virus infections, the underlying mechanisms are poorly understood. For example, although phenotypically distinct populations of memory CD4+ T cells have been identified in different secondary lymphoid tissues, it is not known which subpopulations mediate protective cellular immunity. In this report, we demonstrate that virus-specific CD4+ T cells persist in the lung tissues and airways for several months after Sendai virus infection of C57BL/6 mice. A large proportion of these cells possess a highly activated phenotype (CD44hi, CD62Llo, CD43hi, and CD25hi) and express immediate effector function as indicated by the production of interferon γ after a 5-h restimulation in vitro. Furthermore, intratracheal adoptive transfer of lung memory cells into β2m-deficient mice demonstrated that lung-resident virus-specific CD4+ T cells mediated a substantial degree of protection against secondary virus infection. Taken together, these data demonstrate that activated memory CD4+ T cells persisting at mucosal sites play a critical role in mediating protective cellular immunity.

scholarly journals CD4+T Cells: Differentiation and Functions

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Rishi Vishal Luckheeram ◽  
Rui Zhou ◽  
Asha Devi Verma ◽  
Bing Xia
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Cytokine Signaling ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 17 ◽  
Differentiated Cells ◽  
Follicular Helper ◽  
Follicular Helper T Cell

CD4+T cells are crucial in achieving a regulated effective immune response to pathogens. Naive CD4+T cells are activated after interaction with antigen-MHC complex and differentiate into specific subtypes depending mainly on the cytokine milieu of the microenvironment. Besides the classical T-helper 1 and T-helper 2, other subsets have been identified, including T-helper 17, regulatory T cell, follicular helper T cell, and T-helper 9, each with a characteristic cytokine profile. For a particular phenotype to be differentiated, a set of cytokine signaling pathways coupled with activation of lineage-specific transcription factors and epigenetic modifications at appropriate genes are required. The effector functions of these cells are mediated by the cytokines secreted by the differentiated cells. This paper will focus on the cytokine-signaling and the network of transcription factors responsible for the differentiation of naive CD4+T cells.

scholarly journals Bcl6 Expressing Follicular Helper CD4 T Cells Are Fate Committed Early and Have the Capacity To Form Memory

2013 ◽  
Vol 190 (8) ◽  
pp. 4014-4026 ◽  
Author(s):  
Youn Soo Choi ◽  
Jessica A. Yang ◽  
Isharat Yusuf ◽  
Robert J. Johnston ◽  
Jason Greenbaum ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Follicular Helper
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