scholarly journals Induction of CD4+ T-Cell-Independent Immunoglobulin Responses by Inactivated Influenza Virus

2000 ◽  
Vol 74 (11) ◽  
pp. 4999-5005 ◽  
Author(s):  
Zhiyi Sha ◽  
Richard W. Compans
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cd4 T Cell ◽  
Double Negative ◽  
Class Switching ◽  
Lethal Infection ◽  
Deficient Mice ◽  
Αβ T Cells

ABSTRACT Through cognate interaction between antigen-specific B-cell and CD4+ αβ T cells, the CD4+ αβ T cells secrete cytokines that initiate immunoglobulin (Ig) class switching from IgM to IgG. In this study, we show that formalin-inactivated influenza PR8 virus induces virus-specific IgM and IgG responses in the absence of CD4+ T cells and that all four subclasses of IgG are produced. The immunized CD4-deficient mice were also found to be completely protected against lethal infection with live, pathogenic influenza virus. The ability of CD4+ T-cell-deficient mice to generate these IgG responses was not found to be impaired when these mice were depleted of CD8+ T cells with an anti-CD8 monoclonal antibody. In contrast, αβ T-cell-deficient mice (TCRβ−/−) were not found to produce significant amounts of IgG upon immunization with formalin-inactivated PR8 virus. These results suggest that CD4− CD8−double-negative αβ T cells are playing a role in regulating Ig class switching in the absence of CD4+ T cells.

Overlapping functions of human CD3δ and mouse CD3γ in αβ T-cell development revealed in a humanized CD3γ-deficient mouse

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3420-3427 ◽  
Author(s):  
Edgar Fernández-Malavé ◽  
Ninghai Wang ◽  
Manuel Pulgar ◽  
Wolfgang W. A. Schamel ◽  
Balbino Alarcón ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Double Negative ◽  
Wild Type ◽  
Thymocyte Development ◽  
Double Positive ◽  
Deficient Mice ◽  
Αβ T Cells

Abstract Humans lacking the CD3γ subunit of the pre-TCR and TCR complexes exhibit a mild αβ T lymphopenia, but have normal T cells. By contrast, CD3γ-deficient mice are almost devoid of mature αβ T cells due to an early block of intrathymic development at the CD4–CD8– double-negative (DN) stage. This suggests that in humans but not in mice, the highly related CD3δ chain replaces CD3γ during αβ T-cell development. To determine whether human CD3δ (hCD3δ) functions in a similar manner in the mouse in the absence of CD3γ, we introduced an hCD3δ transgene in mice that were deficient for both CD3δ and CD3γ, in which thymocyte development is completely arrested at the DN stage. Expression of hCD3δ efficiently supported pre-TCR–mediated progression from the DN to the CD4+CD8+ double-positive (DP) stage. However, αβTCR-mediated positive and negative thymocyte selection was less efficient than in wild-type mice, which correlated with a marked attenuation of TCR-mediated signaling. Of note, murine CD3γ-deficient TCR complexes that had incorporated hCD3δ displayed abnormalities in structural stability resembling those of T cells from CD3γ-deficient humans. Taken together, these data demonstrate that CD3δ and CD3γ play a different role in humans and mice in pre-TCR and TCR function during αβ T-cell development.

CD4+ T-Cell Converted Double Negative T-Cells Suppress B-Cells Proliferation and IGG Production in Mice.

2014 ◽  
Vol 98 ◽  
pp. 391
Author(s):  
W. Li ◽  
X. Zhao ◽  
Y. Tian ◽  
W. Shi ◽  
X. Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cd4 T Cell ◽  
Double Negative ◽  
Double Negative T Cells

scholarly journals Infection of HLA-DR1 Transgenic Mice with a Human Isolate of Influenza A Virus (H1N1) Primes a Diverse CD4 T-Cell Repertoire That Includes CD4 T Cells with Heterosubtypic Cross-Reactivity to Avian (H5N1) Influenza Virus

2009 ◽  
Vol 83 (13) ◽  
pp. 6566-6577 ◽  
Author(s):  
Katherine A. Richards ◽  
Francisco A. Chaves ◽  
Andrea J. Sant
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Cd4 T Cells ◽  
Cross Reactivity ◽  
Cd4 T Cell ◽  
Ns1 Protein ◽  
Infected Cells

ABSTRACT The specificity of the CD4 T-cell immune response to influenza virus is influenced by the genetic complexity of the virus and periodic encounters with variant subtypes and strains. In order to understand what controls CD4 T-cell reactivity to influenza virus proteins and how the influenza virus-specific memory compartment is shaped over time, it is first necessary to understand the diversity of the primary CD4 T-cell response. In the study reported here, we have used an unbiased approach to evaluate the peptide specificity of CD4 T cells elicited after live influenza virus infection. We have focused on four viral proteins that have distinct intracellular distributions in infected cells, hemagglutinin (HA), neuraminidase (NA), nucleoprotein, and the NS1 protein, which is expressed in infected cells but excluded from virion particles. Our studies revealed an extensive diversity of influenza virus-specific CD4 T cells that includes T cells for each viral protein and for the unexpected immunogenicity of the NS1 protein. Due to the recent concern about pandemic avian influenza virus and because CD4 T cells specific for HA and NA may be particularly useful for promoting the production of neutralizing antibody to influenza virus, we have also evaluated the ability of HA- and NA-specific CD4 T cells elicited by a circulating H1N1 strain to cross-react with related sequences found in an avian H5N1 virus and find substantial cross-reactivity, suggesting that seasonal vaccines may help promote protection against avian influenza virus.

Interleukin-2 Enhances the Regulatory Functions of CD4+T Cell-Derived CD4−CD8− Double Negative T Cells

2016 ◽  
Vol 36 (8) ◽  
pp. 499-505 ◽  
Author(s):  
Min Cong ◽  
Tianhui Liu ◽  
Dan Tian ◽  
Hongbo Guo ◽  
Ping Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Cd4 T Cell ◽  
Double Negative ◽  
Double Negative T Cells ◽  
Regulatory Functions

scholarly journals Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells

2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Guangyong Sun ◽  
Xiaojing Sun ◽  
Wei Li ◽  
Kai Liu ◽  
Dan Tian ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Critical Role ◽  
Cd4 T Cell ◽  
Double Negative ◽  
Double Negative T Cells

scholarly journals Innate IFNγ is essential for systemic Chlamydia control while CD4 T cell-dependent IFNγ production is highly redundant in the female reproductive tract

2020 ◽  
Author(s):  
Miguel A.B. Mercado ◽  
Wuying Du ◽  
Priyangi A. Malaviarachchi ◽  
Jessica I. Gann ◽  
Lin-Xi Li
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Reproductive Tract ◽  
Early Stage ◽  
Female Reproductive Tract ◽  
Cd4 T Cell ◽  
Bacterial Killing ◽  
Group I ◽  
Deficient Mice

AbstractProtective immunity to the obligate intracellular bacterium Chlamydia is thought to rely on CD4 T cell-dependent IFNγ production. Nevertheless, whether IFNγ is produced by other cellular source during Chlamydia infection and how CD4 T cell-dependent and -independent IFNγ contribute differently to host resistance has not been carefully evaluated. In this study, we dissect the requirements of IFNγ produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal inoculation, IFNγ-deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFNγ and CD4 T cells in host defense against Chlamydia. In Rag-deficient mice, IFNγ produced by innate lymphocytes (ILCs) accounted for early bacterial containment and prolonged survival in the absence of adaptive immunity. Although group I ILCs are potent IFNγ producers, we found that mature NK cells and ILC1 were not the sole source for innate IFNγ in response to Chlamydia. T cell adoptive transfer experiments revealed that WT and IFNγ-deficient CD4 T cells were equally capable of mediating effective bacterial killing in the FRT during the early stage of Chlamydia infection. Together, our results revealed that innate IFNγ is essential for preventing systemic Chlamydia dissemination, whereas IFNγ produced by CD4 T cells is largely dispensable at the FRT mucosa.

scholarly journals Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 220 ◽  
Author(s):  
Zackery A. G. Knowlden ◽  
Katherine A. Richards ◽  
Savannah A. Moritzky ◽  
Andrea J. Sant
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cd4 T Cells ◽  
H1n1 Influenza ◽  
Primary Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Peptide Epitope ◽  
Ha Protein

Antibodies specific for the hemagglutinin (HA) protein of influenza virus are critical for protective immunity to infection. Our studies show that CD4 T cells specific for epitopes derived from HA are the most effective in providing help for the HA-specific B cell responses to infection and vaccination. In this study, we asked whether HA epitopes recognized by CD4 T cells in the primary response to infection are equally distributed across the HA protein or if certain segments are enriched in CD4 T cell epitopes. Mice that collectively expressed eight alternative MHC (Major Histocompatibility Complex) class II molecules, that would each have different peptide binding specificities, were infected with an H1N1 influenza virus. CD4 T cell peptide epitope specificities were identified by cytokine EliSpots. These studies revealed that the HA-specific CD4 T cell epitopes cluster in two distinct regions of HA and that some segments of HA are completely devoid of CD4 T cell epitopes. When located on the HA structure, it appears that the regions that most poorly recruit CD4 T cells are sequestered within the interior of the HA trimer, perhaps inaccessible to the proteolytic machinery inside the endosomal compartments of antigen presenting cells.

Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4336-4343 ◽  
Author(s):  
Josef Kurtz ◽  
Juanita Shaffer ◽  
Ariadne Lie ◽  
Natalie Anosova ◽  
Gilles Benichou ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Cd4 T Cells ◽  
Marrow Transplantation ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance

Abstract Anti-CD154 (CD40L) monoclonal antibody (mAb) plus bone marrow transplantation (BMT) in mice receiving CD8 cell-depleting mAb leads to long-term mixed hematopoietic chimerism and systemic donor-specific tolerance through peripheral and central deletional mechanisms. However, CD4+ T-cell tolerance is demonstrable in vitro and in vivo rapidly following BMT, before deletion of donor-reactive CD4 cells is complete, suggesting the involvement of other mechanisms. We examined these mechanisms in more detail. Spot enzyme-linked immunosorbent (ELISPOT) analysis revealed specific tolerization (within 4 to 15 days) of both T helper 1 (Th1) and Th2 cytokine responses to the donor, with no evidence for cytokine deviation. Tolerant lymphocytes did not significantly down-regulate rejection by naive donor-reactive T cells in adoptive transfer experiments. No evidence for linked suppression was obtained when skin expressing donor alloantigens in association with third-party alloantigens was grafted. T-cell receptor (TCR) transgenic mixing studies revealed that specific peripheral deletion of alloreactive CD4 T cells occurs over the first 4 weeks following BMT with anti-CD154. In contrast to models involving anti-CD154 without BMT, BMT with anti-CD154 leads to the rapid induction of anergy, followed by deletion of pre-existing donor-reactive peripheral CD4+ T cells; the rapid deletion of these cells obviates the need for a regulatory cell population to suppress CD4 cell-mediated alloreactivity. (Blood. 2004;103:4336-4343)

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