scholarly journals CD24 Expression on T Cells Is Required for Optimal T Cell Proliferation in Lymphopenic Host

2004 ◽  
Vol 200 (8) ◽  
pp. 1083-1089 ◽  
Author(s):  
Ou Li ◽  
Pan Zheng ◽  
Yang Liu
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Costimulatory Molecules ◽  
T Cell Proliferation ◽  
Homeostatic Proliferation ◽  
Histocompatibility Complex ◽  
Targeted Mutation ◽  
Reduced Rate

It is well established that T lymphocytes undergo homeostatic proliferation in lymphopenic environment. The homeostatic proliferation requires recognition of the major histocompatibility complex on the host. Recent studies have demonstrated that costimulation-mediated CD28, 4-1BB, and CD40 is not required for T cell homeostatic proliferation. It has been suggested that homeostatic proliferation is costimulation independent. Here, we report that T cells from mice with a targeted mutation of CD24 have a remarkably reduced rate of proliferation when adoptively transferred into syngeneic lymphopenic hosts. The reduced proliferation cannot be attributed to abnormal survival and homing properties of the CD24-deficient T cells. T cell proliferation in allogeneic hosts is less affected by this mutation. These results demonstrate a novel function of CD24 expressed on T cells. Thus, although distinct costimulatory molecules are involved in antigen-driven proliferation and homeostatic proliferation, both processes can be modulated by costimulatory molecules.

scholarly journals Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice.

1992 ◽  
Vol 175 (6) ◽  
pp. 1707-1715 ◽  
Author(s):  
E Barzaga-Gilbert ◽  
D Grass ◽  
S K Lawrance ◽  
P A Peterson ◽  
E Lacy ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Class Ii ◽  
T Cell Proliferation ◽  
Human Class ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Species Specific

Murine T cell responses to human class II major histocompatibility complex (MHC) molecules were shown to be a minimum of 20-70-fold lower than responses to allogeneic molecules. Transgenic mice expressing slightly below normal (75-95%) or very high (250-380%) cell surface levels of human CD4 were utilized to determine whether this was due to a species-specific interaction between murine CD4 and class II molecules. Human CD4 was shown to function in signal transduction events in murine T cells based on the ability of anti-human CD4 antibody to synergize with suboptimal doses of anti-murine CD3 antibody in stimulating T cell proliferation. In mice expressing lower levels of human CD4, T cell responses to human class II molecules were enhanced up to threefold, whereas allogeneic responses were unaltered. In mice expressing high levels of human CD4, responses to human class II molecules were enhanced at least 10-fold, whereas allogeneic responses were between one and three times the level of normal responses. The relatively greater enhancement of the response to human class II molecules in both lines argues for a preferential interaction between human CD4 and human class II molecules. In mice expressing lower levels of human CD4, responses to human class II molecules were blocked by antibodies to CD4 of either species, indicating participation by both molecules. In mice expressing high levels of human CD4, responses to both human and murine class II molecules were almost completely blocked with anti-human CD4 antibody, whereas anti-murine CD4 antibody had no effect. However, anti-murine CD4 continued to synergize with anti-CD3 in stimulating T cell proliferation in these mice. Thus, overexpression of human CD4 selectively impaired the ability of murine CD4 to assist in the process of antigen recognition. The ability of human CD4 to support a strong allogeneic response under these conditions indicates that this molecule can interact with murine class II molecules to a significant extent. Despite the fact that human CD4 appeared to be the only functional coreceptor in these mice, responses to human class II molecules were still much lower than those to murine class II alloantigens. This indicates that species-specific interactions between class II molecules and CD4 expressed on peripheral T cells are not sufficient to account for the low xenogeneic response and that intrinsic differences in T cell receptor structures or the need for species specificity in the interaction between CD4 and class II molecules during positive selection are also important.

scholarly journals Bone marrow–based homeostatic proliferation of mature T cells in nonhuman primates: implications for AIDS pathogenesis

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 612-621 ◽  
Author(s):  
Mirko Paiardini ◽  
Barbara Cervasi ◽  
Jessica C. Engram ◽  
Shari N. Gordon ◽  
Nichole R. Klatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Homeostatic Proliferation ◽  
T Cell Homeostasis ◽  
Cell Homeostasis

AbstractBone marrow (BM) is the key hematopoietic organ in mammals and is involved in the homeostatic proliferation of memory CD8+ T cells. Here we expanded on our previous observation that BM is a preferential site for T-cell proliferation in simian immunodeficiency virus (SIV)–infected sooty mangabeys (SMs) that do not progress to AIDS despite high viremia. We found high levels of mature T-cell proliferation, involving both naive and memory cells, in healthy SMs and rhesus macaques (RMs). In addition, we observed in both species that lineage-specific, BM-based T-cell proliferation follows antibody-mediated in vivo CD4+ or CD8+ T-cell depletion, thus indicating a role for the BM in maintaining T-cell homeostasis under depleting circumstances. We also observed that, in SIV-infected SMs, but not RMs, the level of proliferation of BM-based CD4+ T cells is higher than that of circulating CD4+ T cells. Interestingly, limited BM-based CD4+ T-cell proliferation was found in SIV-infected SMs with low CD4+ T-cell counts, suggesting a regenerative failure in these animals. Collectively, these results indicate that BM is involved in maintaining T-cell homeostasis in primates and suggest a role for BM-based CD4+ T-cell proliferation in determining the benign nature of natural SIV infection of SMs.

Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection

2006 ◽  
Vol 291 (2) ◽  
pp. G253-G259 ◽  
Author(s):  
Ahmed Metwali ◽  
Tommy Setiawan ◽  
Arthur M. Blum ◽  
Joseph Urban ◽  
David E. Elliott ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Lamina Propria ◽  
T Cell Proliferation ◽  
Cell Contact ◽  
Heligmosomoides Polygyrus ◽  
Histocompatibility Complex ◽  
Antigen Presenting

This study determined whether Heligmosomoides polygyrus induces intestinal regulatory T cells. Splenic T cells proliferate strongly when cultured with anti-CD3 and antigen-presenting cells (APC). Lamina propria T cells from mice with H. polygyrus mixed with normal splenic T cells from uninfected mice inhibited proliferation over 90%. Lamina propria T cells from mice without H. polygyrus only modestly affected T cell proliferation. The worm-induced regulatory T cell was CD8+ and required splenic T cell contact to inhibit proliferation. The regulation also was IL-10 independent, but TAP-dependent, suggesting that it requires major histocompatibility complex (MHC) class I interaction. Additional studies employed mice with transgenic T cells that did not express functional TGF-β receptors. The lamina propria T regulator inhibited proliferation of these transgenic T cells nearly 100%, suggesting that TGF-β signaling via the T cell was not required. CD8+ T cells were needed for worms to reverse piroxicam-induced colitis in Rag mice (T and B cell deficient) reconstituted with IL-10−/− T cells. Thus H. polygyrus induces a regulatory CD8+ lamina propria T cell that inhibits T cell proliferation and that appears to have a role in control of colitis.

scholarly journals Immunogenic and Protective Potential of Mutans Streptococcal Glucosyltransferase Peptide Constructs Selected by Major Histocompatibility Complex Class II Allele Binding

2006 ◽  
Vol 75 (2) ◽  
pp. 915-923 ◽  
Author(s):  
S. Culshaw ◽  
K. LaRosa ◽  
H. Tolani ◽  
X. Han ◽  
J. W. Eastcott ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Dental Caries ◽  
Functional Significance ◽  
Class Ii ◽  
Binding Activity ◽  
T Cell Proliferation ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

ABSTRACT Mutans streptococcal glucosyltransferases (GTF) have been demonstrated to be effective components of dental caries vaccines. We had previously selected peptide subunits of GTF for vaccine development based on putative functional significance and conservation of GTF primary structure among enzyme isoforms. In this study, 20 20-mer linear GTF peptides were synthesized, 17 identified on the basis of the highest potential major histocompatibility complex (MHC) class II-binding activity using computer-generated algorithms (Epimatrix and ProPred) and 3 with previously demonstrated functional significance. The immunoreactivities of these peptides were explored with rodent systems. Sera from GTF-immunized rats, assessed for binding to linear peptides by enzyme-linked immunosorbent assay, demonstrated immunoglobulin G antibody reactivity with peptides 6 and 11 and a T-cell proliferation response to peptides 6, 9, 11, and 16. Multiple antigenic peptide (MAP) constructs were synthesized from promising linear sequences. Rats that were immunized with MAP 7, 11, or 16, respectively, responded well to the immunizing MAP. Most importantly, a robust immune response (antibody and T-cell proliferation) was observed to native GTF following MAP 11 (amino acids 847 to 866; VVINNDKFVSWGITDFEM) immunization. This response inhibited GTF enzyme function. Two dental caries pathogenesis experiments were performed wherein rats were immunized with MAP constructs 11, 16, and/or 11 plus 16, followed by infection with cariogenic Streptococcus sobrinus. In both experiments cariogenic bacterial recoveries were reduced relative to total streptococci in the MAP 11- and MAP 11 plus 16-immunized groups, and the extent of dental caries was also significantly reduced in these groups. Thus, we have identified a peptide with projected avid MHC-binding activity that elicited immunoreactivity with native GTF and demonstrated protection against dental caries infection after immunization, implying that this peptide may be important in a subunit dental caries vaccine.

scholarly journals Coordinate Suppression of Superantigen-Induced Cytokine Production and T-Cell Proliferation by a Small Nonpeptidic Inhibitor of Class II Major Histocompatibility Complex and CD4 Interaction

2000 ◽  
Vol 44 (4) ◽  
pp. 1067-1069 ◽  
Author(s):  
Teresa Krakauer
Keyword(s):  
Cell Proliferation ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Class Ii ◽  
T Cell Proliferation ◽  
Major Histocompatibility ◽  
Peripheral Blood Mononuclear ◽  
Histocompatibility Complex

ABSTRACT Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). TJU103, a small nonpeptidic molecule that blocks the interaction between major histocompatibility complex class II and CD4 molecules inhibited SE-stimulated T-cell proliferation (by 92%) and production of tumor necrosis factor, interleukin 1β, interleukin 6, and gamma interferon (by 66, 56, 76, and 72%, respectively) by human peripheral blood mononuclear cells. These data suggest that TJU103 may be useful for mitigating the pathogenic effects of SE.

The Role of T Cell Costimulation by CD80 in the Immune Response to Human Waldenstrom’s Macroglobulinemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4743-4743
Author(s):  
Wei Cai ◽  
Zhuoru Liu ◽  
Eckhardt Podack ◽  
Paul Harris ◽  
Gwen Nichols
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Plasmid Dna ◽  
Costimulatory Molecules ◽  
T Cell Proliferation ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Waldenstrom’s macroglobulinemia (WM) is characterized by the presence of monoclonal serum IgM and bone marrow infiltration by lymphoplasmacytoid cells. The transforming event(s) and mechanisms underlying disease progression remain uncertain. The rationale behind the use of allogeneic tumor cell lines as therapeutic vaccines is that multiple antigens shared by both the immunizing line and the patient’s tumor are presented by shared human leukocyte antigen (HLA) molecules. Most tumor cells are of poor immunogenicity and do not effectively induce antigen-specific immune responses. This is frequently due to low densities of HLA/antigen complexes and a lack of costimulatory molecules. CD80 appears to be the most efficient costimulatory molecule in humans. In this experiment, we introduced the CD80 gene into allogeneic WM cells to effect in vitro stimulation of T lymphocytes. A human WM cell line, WM103 (HLA-A2 positive, HLA-A1 and CD80 negative), kindly provided by Dr. Al-Katib, and human CD80 plasmid DNA (hB7-pBCMGHis), Dr. E. Podack, were used. 2 ×106 WM103 cells were resuspended in 100 μl of Human B Cell Nucleofector Solution (Amaxa), and 5μg of plasmid DNA. Nucleofector program U-15 used for transfection. Cells were cultured for 48h and harvested. Transfected WM103 cells were examined for expression of CD80 antigen by FACS (FACSCalibur, Becton Dickinson) using PE-conjugated anti-human CD80 (eBioscience). HLA-typed normal mononuclear cells were isolated and used as responders at a density of 1 × 106/well. Irradiated (3000 rads) WM103 cells (5 × 104/well) were used as stimulatosr at four dilutions 1:1, 1:0.5, 1:0.25 and 1: 0.125, incubated for 5 days, and treated for 18h with 1 μCi [3H] thymidine per well. liquid scintillization counting was performed in triplicate. Successful CD80 transfection into WM103 cells. CD80 transfection into WM103 cells was confirmed by using flow cytometry. Successful CD80 transfection into WM103 cells. CD80 transfection into WM103 cells was confirmed by using flow cytometry. CD80 transfection induced strong T-cell proliferation in allogeeneic MLTC of heallthy donors. CD80 transfected WM103 cells can stimulate proliferation of allogeneic T-cells from adult blood. CD80 transfection induced strong T-cell proliferation in allogeeneic MLTC of heallthy donors. CD80 transfected WM103 cells can stimulate proliferation of allogeneic T-cells from adult blood. It has been established that T cell activation by presenting cells (APC) requires two types of signals: the first generated from T cell receptor engagement with specific antigen, and the second by constimulatory molecules. Interaction of CD80 on APCs with their natural ligand on T cells has a crucial role in costimulation and maintenance of T cell immunity. CD80 transfected allogeneic or autologous cells have not been reported in patients with WM, although similar vaccines have shown good activity in other human studies. In this report, transfection of CD80 into WM103 cells induced an allogeneic response in T cells from healthy donors, demonstrating that CD80 expression can lead to accessory cell-independent activation of native T cells. These experiments support the hypothesis that lack of expression of T-cell costimulatory molecules contributes to WM escape from immune surveillance, and provide preliminary data for the use of CD80 transfection in the immunotherapy of human WM.

Type D SRV‐2 virus‐specific CD8 + and CD4 ‐ CD8 ‐ T cells that regulate virus‐induced T cell proliferation in Celebes macaques

1993 ◽  
Vol 22 (2-3) ◽  
pp. 80-85
Author(s):  
A. Malley ◽  
N. Pangares ◽  
S.K. Mayo ◽  
M. Zeleny‐Pooley ◽  
J.V. Torres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Proliferation ◽  
Type D

scholarly journals Costimulation by B7 Modulates Specificity of Cytotoxic T Lymphocytes: A Missing Link That Explains Some Bystander T Cell Activation

1997 ◽  
Vol 186 (10) ◽  
pp. 1787-1791 ◽  
Author(s):  
Pan Zheng ◽  
Yang Liu
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
T Cell Proliferation ◽  
Target Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

It has been proposed that some bystander T cell activation may in fact be due to T cell antigen receptor (TCR) cross-reactivity that is too low to be detected by the effector cytotoxic T lymphocyte (CTL). However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL. Here we report that transgenic T cells expressing a T cell receptor to influenza virus A/NT/68 nucleoprotein (NP) 366-374:Db complexes clonally expand and become effector CTLs in response to homologous peptides from either A/PR8/34 (H1N1), A/AA/60 (H2N2), or A/NT/68 (H3N2). However, the effector T cells induced by each of the three peptides kill target cells pulsed with NP peptides from the H3N2 and H2N2 viruses, but not from the H1N1 virus. Thus, NP366–374 from influenza virus H1N1 is the first TCR ligand that can induce T cell proliferation and differentiation without being recognized by CTLs. Since induction of T cell proliferation was mediated by antigen-presenting cells that express costimulatory molecules such as B7, we investigated if cytolysis of H1N1 NP peptide–pulsed targets can be restored by expressing B7-1 on the target cells. Our results revealed that this is the case. These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

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