scholarly journals The contribution of L3T4+ T cells to lymphoproliferation and autoantibody production in MRL-lpr/lpr mice.

1988 ◽  
Vol 167 (5) ◽  
pp. 1713-1718 ◽  
Author(s):  
T J Santoro ◽  
J P Portanova ◽  
B L Kotzin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Treatment ◽  
Cell Subset ◽  
Dramatic Reduction ◽  
Autoantibody Production ◽  
T Cell Subset

The current study examines the role of the L3T4 T cell subset in the development of lupus-like autoimmunity and lymphoproliferation in lpr-bearing mice. Chronic treatment of MRL-lpr/lpr mice with anti-L3T4 antibody beginning at 4 wk old was found to markedly decrease the production of IgG anti-DNA and antihistone antibodies, while having no effect on IgM autoantibodies. A dramatic reduction in splenomegaly and lymphadenopathy was also observed coincident with a decrease in the percentage and total number of Thy-1+, B220+ cells. Together, the data suggest an important role for L3T4+ T cells in the pathogenesis of disease in lpr mice and provide further evidence that a requirement for the L3T4 subset may be a common feature of murine autoimmunity.

scholarly journals Critical role of the CD44lowCD62Llow CD8+ T cell subset in restoring antitumor immunity in aged mice

2021 ◽  
Vol 118 (23) ◽  
pp. e2103730118
Author(s):  
Yuka Nakajima ◽  
Kenji Chamoto ◽  
Takuma Oura ◽  
Tasuku Honjo
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Critical Role ◽  
Cell Subset ◽  
Effector Memory ◽  
T Cell Subset ◽  
Aged Mice ◽  
Age Related

CD8+ T cells play a central role in antitumor immune responses that kill cancer cells directly. In aged individuals, CD8+ T cell immunity is strongly suppressed, which is associated with cancer and other age-related diseases. The mechanism underlying this age-related decrease in immune function remains largely unknown. This study investigated the role of T cell function in age-related unresponsiveness to PD-1 blockade cancer therapy. We found inefficient generation of CD44lowCD62Llow CD8+ T cell subset (P4) in draining lymph nodes of tumor-bearing aged mice. In vitro stimulation of naive CD8+ T cells first generated P4 cells, followed by effector/memory T cells. The P4 cells contained a unique set of genes related to enzymes involved in one-carbon (1C) metabolism, which is critical to antigen-specific T cell activation and mitochondrial function. Consistent with this finding, 1C-metabolism–related gene expression and mitochondrial respiration were down-regulated in aged CD8+ T cells compared with young CD8+ T cells. In aged OVA-specific T cell receptor (TCR) transgenic mice, ZAP-70 was not activated, even after inoculation with OVA-expressing tumor cells. The attenuation of TCR signaling appeared to be due to elevated expression of CD45RB phosphatase in aged CD8+ T cells. Surprisingly, strong stimulation by nonself cell injection into aged PD-1–deficient mice restored normal levels of CD45RB and ameliorated the emergence of P4 cells and 1C metabolic enzyme expression in CD8+ T cells, and antitumor activity. These findings indicate that impaired induction of the P4 subset may be responsible for the age-related resistance to PD-1 blockade, which can be rescued by strong TCR stimulation.

CD4+CD25+ Regulatory T Cells Control Induction of Autoimmune Hemolytic Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 579-579
Author(s):  
Karina Yazdanbakhsh ◽  
Amina Mqadmi ◽  
Xiaoying Zheng
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Repeated Injection ◽  
Autoantibody Production

Abstract Autoimmune Hemolytic anemia (AIHA) is the result of increased destruction of red blood cells (RBCs) due to the production of antibodies against self antigens. Anemia can be severe and life-threatening. The underlying mechanism of autoimmunity is the result of breakdown of immune tolerance, but the molecular and cellular basis for the induction of AIHA remains to be fully defined. To further our understanding of mechanisms that trigger AIHA, we used the Marshall-Clarke and Playfair model of murine AIHA. Anemia is induced by repeated injection of rat RBCs resulting in development of erythrocyte autoantibodies as well as rat-specific immunoglobulins. The severity of the autoimmune disease is strain dependent. We found that in about 20–30% of C57/Bl6 mice repeatedly immunized with washed rat RBCs, there is breakdown of tolerance and development of pathogenic autoantibodies resulting in decreased hematocrit, reticulocytosis and increased destruction of transfused syngeneic mouse RBCs. To identify the immunological factors contributing to the incidence of AIHA, we analyzed the role of specific T regulatory subsets in controlling AIHA in C57/Bl6 mice. Previous studies documented that depletion of selected regulatory CD4+ T cell subsets (CD25+, CD62L+ and CD45RBlow) can induce different degrees of autoimmune disorders. However, the nature of the regulatory T cell subset in the induction of AIHA has not yet been studied. To test the role of CD25+ T regulatory cells in the induction of AIHA, 10 week old C57/Bl6 mice (n=10) were treated with 500 μg of anti-CD25 antibody six hours prior to immunization with rat RBCs on a weekly basis for four weeks. Following this repeated challenge the incidence of AIHA increased from 20 to 90%. Treatment with isotype control antibody prior to weekly injections of rat RBCs for four weeks resulted in the expected 20% incidence of AIHA. Furthermore, weekly treatment with anti-CD25 alone for four weeks did not result in development of AIHA, indicating that the depletion of CD25 cells in combination with rat RBC stimulus was important for the development AIHA. To test whether anti-CD25 treatment also increased the levels of autoantibodies directed against other non-erythroid antigens, we measured the levels of antibodies to double stranded DNA (anti-ds DNA) characteristic of systemic autoimmune disease and found significantly elevated levels in anti-CD25/rat RBC immunized mice, as compared to control mice treated with rat RBCs alone. Interestingly, treatment with anti-CD25 alone did not result in increased levels of anti-ds DNA, indicating that selective depletion of CD25+ does not result in the development of autoimmunity and that an additional signal is required to activate autoreactivity. In addition, the levels of alloantibodies against rat RBCs in anti-CD25/rat RBC immunized mice were elevated as compared to mice treated with rat RBCs alone, consistent with a heightened immune hypersensitive state. Importantly, adoptive transfer of purified splenic population of CD4+CD25+ from mice that had undergone weekly injections of rat erythrocytes for 12 weeks into naïve C57/Bl6 mice (n=5) prevented the induction of autoantibody production whereas transfer of CD4+CD25-T cells into naïve mice (n=6) significantly elevated the autoantibody levels following weekly immunization with rat RBCs. These findings emphasize an important suppressive role for CD4+CD25+ in prevention of AIHA. Altogether, our data provide new insight regarding the mechanism for breakdown of tolerance in antibody-mediated autoimmunes disease which may help to establish therapeutic strategies for treatment of AIHA.

CD4 T Cell Subset Profiling in Biliary Atresia Reveals ICOS- Regulatory T Cells as a Favourable Prognostic Factor

2018 ◽  
Author(s):  
Shuhao Zhang ◽  
Shyamal Goswami ◽  
Jiaqiang Ma ◽  
Lu Meng ◽  
Youping Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Prognostic Factor ◽  
Regulatory T Cells ◽  
Biliary Atresia ◽  
Cell Subset ◽  
Cd4 T Cell ◽  
T Cell Subset

scholarly journals Human CD8+ T-cells Recognizing Peptides from Mycobacterium tuberculosis (Mtb) Presented by HLA-E Have an Unorthodox Th2-like, Multifunctional, Mtb Inhibitory Phenotype and Represent a Novel Human T-cell Subset

2015 ◽  
Vol 11 (3) ◽  
pp. e1004671 ◽  
Author(s):  
Krista E. van Meijgaarden ◽  
Mariëlle C. Haks ◽  
Nadia Caccamo ◽  
Francesco Dieli ◽  
Tom H. M. Ottenhoff ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
T Cell Subset ◽  
Human T Cell

scholarly journals Induction of autoreactive B cells allows priming of autoreactive T cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1433-1439 ◽  
Author(s):  
R H Lin ◽  
M J Mamula ◽  
J A Hardin ◽  
C A Janeway
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cytochrome C ◽  
Autoantibody Production ◽  
Autoreactive T Cells ◽  
Human Cytochrome ◽  
Self Tolerance ◽  
Human Cytochrome C

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

scholarly journals Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells.

1983 ◽  
Vol 158 (3) ◽  
pp. 649-669 ◽  
Author(s):  
H Kawanishi ◽  
L Saltzman ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Present Report ◽  
Protein A ◽  
Cell Subset ◽  
Terminal Differentiation ◽  
Lymphoid Tissues ◽  
T Cell Subset ◽  
Iga Production

Our previous studies indicated that cloned T cells obtained from Peyer's patches (PP) (Lyt-1+, 2-, Ia+, and H-2K/D+) evoked immunoglobulin (Ig) class switching of PP B cells from sIgM to sIgA cells in vitro; however, these switch T cells could not in themselves provide optimal help for the differentiation of postswitch sIgA-bearing PP B cells to IgA-secreting cells. Thus, in the present report we described studies focused on mechanisms regulating terminal differentiation of the postswitch PP sIgA-bearing B cells. First, to explore the effect of T cell-derived B cell differentiation factor(s) (BCDF) and macrophage factor(s) (MF) on the terminal maturation of PP B cells, LPS-stimulated PP B cells were co-cultured for 7 d with cloned T cells in the presence or absence of the above factors. In the absence of PP cloned T cells the BCDF and MF had only a modest effect on IgA production, whereas in the presence of PP, but not spleen cloned T cells, IgA production was increased. Next, to investigate the effect of T cells derived from a gut-associated lymphoid tissue (GALT), mesenteric lymph nodes (MLN), as well as from spleen on terminal differentiation of postswitch sIgA PP B cells, LPS-driven PP B cells were precultured with the cloned T cells to induce a switch to sIgA, and subsequently cultured with MLN or spleen T cells or a Lyt-2+-depleted T cell subset in the presence of a T-dependent polyclonal mitogen, staphylococcal protein A. Alternatively, in the second culture period BCDF alone was added, instead of T cells and protein A. Here it was found that B cells pre-exposed to switch T cells from PP, but not spleen, were induced to produce greatly increased amounts of IgA in the presence of protein A and T cells or a Lyt-2+-depleted T cell subset as well as in the presence of BCDF alone. Furthermore, in the presence of BCDF alone many B cells expressed cytoplasmic IgA. These observations strongly support the view that the terminal differentiation of postswitch sIgA B cells is governed by helper T cells and macrophages, or factors derived from such cells. Such cells or factors do not affect preswitch B cells.

scholarly journals Selective anergy of V beta 8+ T cells in human immunodeficiency virus-infected individuals.

1994 ◽  
Vol 179 (2) ◽  
pp. 413-424 ◽  
Author(s):  
G Dadaglio ◽  
S Garcia ◽  
L Montagnier ◽  
M L Gougeon
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Clinical Status ◽  
Interleukin 2 ◽  
Cell Subset ◽  
T Cell Subset ◽  
Immunodeficiency Virus

We have analyzed the V beta usage by CD4+ and CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals in response to an in vitro stimulation with the superantigenic erythrogenic toxin A (ETA) of Streptococcus pyogenes. ETA amplifies specifically CD4+ and CD8+ T cells from control donors expressing the V beta 8 and the V beta 12 elements. When peripheral T cells from asymptomatic HIV-infected individuals were stimulated with ETA, there was a complete lack of activation of the V beta 8+ T cell subset, whereas the V beta 12+ T cell subset responded normally to the superantigen. This V beta-specific anergy, which was also observed in response to staphylococcal enterotoxin E (SEE), affected both CD4+ and CD8+ T cells and represented an intrinsic functional defect rather than a specific lack of response to bacterial superantigens since it was also observed after a stimulation with V beta 8 monoclonal antibodies. The V beta 8 anergic T cells did not express interleukin 2 receptors (IL-2Rs) and failed to proliferate in response to exogenous IL-2 or IL-4, suggesting that this anergy was not a reversible process, at least by the use of these cytokines. The unresponsiveness of the V beta 8 T cell subset is frequent since it was found in 56% of the patients studied, and comparison of the clinical status of responder vs. anergic patients indicated that the only known common factor between them was HIV infection. In addition, it is noteworthy that the anergy of the V beta 8 subset may be a very early phenomenon since it was found in a patient at Centers for Disease Control stage I of the disease. These data provide evidence that a dominant superantigen may be involved in the course of HIV infection and that the contribution of HIV has to be considered.

scholarly journals CXCR5 and ICOS expression identifies a CD8 T-cell subset with TFH features in Hodgkin lymphomas

2018 ◽  
Vol 2 (15) ◽  
pp. 1889-1900 ◽  
Author(s):  
Kieu-Suong Le ◽  
Patricia Amé-Thomas ◽  
Karin Tarte ◽  
Françoise Gondois-Rey ◽  
Samuel Granjeaud ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
T Cell Subset ◽  
Tfh Cells ◽  
Key Points ◽  
Functional Features

Key Points A subset of CD8 T cells in some Hodgkin lymphomas shares phenotypic and functional features with CD4 TFH cells.

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