A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells.

Noelle, Randolph J.; Roy, Michael S.; Shepherd, David M.; Stamenkovic, Ivan; Ledbetter, Jeffrey A.; Aruffo, Alejandro

doi:10.1073/pnas.89.14.6550

Cited by 743 publications

(434 citation statements)

References 29 publications

Supporting

Mentioning

420

Contrasting

Unclassified

Order By: Relevance

“…Recently Shoker et al (32) demonstrated heightened CD154 gene expression in CD4+ T-lymphocytes during acute and chronic renal rejection, which correlated with the severity of rejection. In contrast to other reported results they demonstrated constitutive CD154 gene expression in PBMCs (12,(33)(34)(35)(36)(37).…”

Section: Discussioncontrasting

confidence: 99%

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

Bartlett¹,

McCall²,

Ameratunga³

et al. 2003

American Journal of Transplantation

View full text Add to dashboard Cite

CD40-CD154 and/or CD28-CD80/86 costimulatory blockade induces long-term allograft survival in numerous animal models. Studies examining the expression of costimulatory molecules during acute cellular rejection (ACR) have been limited to renal and cardiac allografts.The aim of this study was to describe the relationship between intragraft costimulatory molecule expression in OLT recipients and ACR. Forty-five liver biopsies were obtained at reperfusion and day 7. Gene and protein expression of CD80, CD86 and CD154 were analyzed by RT-PCR and immunohistochemistry. CD154 protein expression was present in 13 of 18 patients with a RAI score of 4, but in only two of 14 patients with a RAI score of <4. There was a strong association between the RAI score and the presence of CD80 and CD154 immunoreactivity. CD86 protein expression did not correlate with the severity of ACR. In reperfusion biopsies CD154, but not CD80 or CD86, protein expression correlated with the total ischaemic time. There was no association between expression of costimulatory molecule genes and ACR.In conclusion, we have demonstrated an association between CD154 and CD80 protein expression and ACR in orthotopic liver allografts.

show abstract

Section: Discussioncontrasting

confidence: 99%

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

Bartlett¹,

McCall²,

Ameratunga³

et al. 2003

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…The Ad5/F35-IL2 used in this study may allow these problems to be overcome. Similarly, CD40 ligand (CD40L, also known as gp39 and CD154) is essential in T/B cell interaction 49,50 and for maturation of APC. 16,47 For example, the lack of CD40L on T cell leads to X-linked hyper-IgM syndrome, 51 and in many leukemias, T cell anergy has been attributed to defective CD40L expression by the malignant cells.…”

Section: Discussionmentioning

confidence: 99%

Efficient infection of primitive hematopoietic stem cells by modified adenovirus

et al. 2001

View full text Add to dashboard Cite

Almost all studies of adenoviral vector-mediated gene transfer have made use of the adenovirus type 5 (Ad5). Unfortunately, Ad5 has been ineffective at infecting hematopoietic progenitor cells (HPC). Chimeric Ad5/F35 vectors that have been engineered to substitute the shorter-shafted fiber protein from Ad35 can efficiently infect committed hematopoietic cells and we now show highly effective gene transfer to primitive progenitor subsets. An Ad5GFP and Ad5/F35GFP vector was added to CD34 + and CD34 − lineage − (lin − ) HPC. Only 5-20% of CD34 + and CD34 − lin − cells expressed GFP after Ad5 exposure. In contrast, with the Ad5/F35 vector, 30-70% of the CD34 + , 50-70% of the CD34 − lin − and up to 60% of the CD38 − HPC expressed GFP and there was little evident cellular toxicity. Because of these improved results, we

show abstract

“…The first cognate interactions between B cells and CD4 + T cells occur at the interface between the T‐ and B‐cell zones in lymphoid tissues 95. T‐cell‐mediated ligation of CD40 on the B cell triggers B‐cell clonal expansion and differentiation,96 and cytokines produced by the T cell including interleukin (IL)‐21 and IL‐4 promote growth and differentiation and direct Ig class switching 97, 98. Provision of help is dependent on an active two‐way interaction between the B and T cell, with inducible T‐cell costimulatory (ICOS) triggering being important for IL‐21 production99 and IL‐4 production being dependent on signaling lymphocytic activation molecule (SLAM) 100.…”

Section: T Follicular Helper Cells and Their Role In Bnab Inductionmentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

View full text Add to dashboard Cite

SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

show abstract

A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells.

Abstract: CD40 is a B-cell surface molecule that has been shown to induce B-cell growth upon ligation with monoclonal antibodies. This report shows that triggering via CD40 is essential for the activation of resting B cells by helper T cells (Th)

Cited by 743 publications

References 29 publications

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

Efficient infection of primitive hematopoietic stem cells by modified adenovirus

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Contact Info

Product

Resources

About