Apoptosis Induced by Crosslinking of CD4 on Activated Human B Cells

Cutrona, Giovanna; Leanza, Nicolò; Ulivi, Massimo; Majolini, M. Bernardetta; Taborelli, G; Zupo, Simona; Baldari, Cosima T.; Roncella, Silvio; Ferrarini, Manlio

doi:10.1006/cimm.1999.1455

Cited by 10 publications

(8 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although lack of response after depletion of CD4+ T cells is consistent with the interpretation that CD4+ T cells are required, there is the potential that the CD4‐depleting antibody exerted its effect by other mechanisms. First, there are CD4 expressing non‐T‐cell lineages that may be critical for the anti‐PLT response 17‐22 . Second, the mechanisms of CD4+ T‐cell depletion may interfere with the normal way transfused LR‐PLTs are processed (e.g., by saturating macrophages or inducing cytokines).…”

Section: Resultsmentioning

confidence: 99%

“…First, there are CD4 expressing non-T-cell lineages that may be critical for the anti-PLT response. [17][18][19][20][21][22] Second, the mechanisms of CD4+ T-cell depletion may interfere with the normal way transfused LR-PLTs are processed (e.g., by saturating macrophages or inducing cytokines). To control for these possibilities, we utilized a separate experimental approach to assess CD4+ T-cell requirements.…”

Section: Recipient Cd4+ T Cells Are Required For Humoral Alloimmunizamentioning

confidence: 99%

See 1 more Smart Citation

Alloimmunization to transfused platelets requires priming of CD4+ T cells in the splenic microenvironment in a murine model

Gilson

Zimring

2011

Transfusion

View full text Add to dashboard Cite

Background Alloantibodies are a clinically significant sequelae of platelet transfusion, potentially rendering patients refractory to ongoing platelet transfusion support. These antibodies are often IgG class switched, suggesting the involvement of CD4+ T cell help; however, platelet specific CD4+ T cells have not been visualized in vivo and specifics of their stimulation are not completely understood. Study Design and Methods A murine model of alloimmunization to transfused platelets was developed to allow in vivo assessment and characterization of CD4+ T cells specific for platelet MHC alloantigen. Platelets were harvested from BALB/c mice, filter leukoreduced, and transfused into C57BL/6 recipients. Platelet specific CD4+ T cell responses were visualized by using a TCR transgenic mouse that detects peptide from donor MHC I presented on recipient MHC II. Antibody responses were determined by indirect immunofluorescence using BALB/c donor targets. Results C57BL/6 recipients of BALB/c leukoreduced platelet transfusions produced anti-BALB/c antibodies, with proliferation of antigen specific CD4+ T cells seen in the spleen but not lymph nodes or liver. Depletion of recipient CD4+ cells or splenectomy independently abrogated the alloantibody response. Conclusion We report a novel model to study antigen-specific CD4+ T cells during alloimmunization to platelet transfusion. The presented data support a critical role for CD4+ T cell help in the humoral response to platelet transfusion and establish the spleen as a required microenvironment for effective CD4+ T cell priming against donor platelet derived MHC I.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Recipient Cd4+ T Cells Are Required For Humoral Alloimmunizamentioning

confidence: 99%

Alloimmunization to transfused platelets requires priming of CD4+ T cells in the splenic microenvironment in a murine model

Gilson

Zimring

2011

Transfusion

View full text Add to dashboard Cite

show abstract

“…Expression of CD4 on human APC is well known for monocytes and dendritic cells [4,6,7]. In addition, expression of CD4 on human B cells at least at the RNA level has been observed [40][41][42][43]. B cells can be infected by human immunodeficiency virus (HIV) and this infection is inhibited by antibodies with specificity for CD4 despite undetectable surface expression of CD4 [40,42].…”

Section: Discussionmentioning

confidence: 99%

Expression of CD4 on Epstein–Barr Virus‐immortalized B Cells

et al. 2009

View full text Add to dashboard Cite

Human antigen presenting cells commonly express CD4 but the significance of this phenomenon has not been clarified. We analyzed a panel of Epstein–Barr virus‐immortalized B cells (so called lymphoblastoid cell lines, LCL) by using flow cytometry, DNA‐microarray analysis, and reverse transcriptase‐polymerase chain reaction (RT‐PCR). The number of CD4+ cells varied from cell line to cell line but expression of CD4 was detected by flow cytometry and RT‐PCR in all investigated cell lines. To characterize CD4 expressing LCL in more detail, we separated CD4+ and CD4− cells from single cell lines by using immunomagnetic beads. When we cultured sorted CD4+ and CD4− cells, we observed that CD4 expression was stable for several passages. However, the number of CD4+ cells decreased with time in culture. We never observed that CD4− cell lines returned back to a CD4+ phenotype. DNA‐microarray analysis of isolated CD4+ and CD4− cells indicated that the overall gene expression profile of both cell populations was highly similar. In addition, CD4+ and CD4− cells showed the same allostimulatory capacity. CD4+ LCL showed a slightly increased interleukin‐16 induced chemotaxis. Differences in the gene expression profile of CD4+ and CD4− cell lines suggested that loss of CD4 expression occurred during a differentiation step involving achaete–scute complex homolog‐like 1.

show abstract

“…In contrast to freshly isolated, resting human NK cells, activated human NK cells can express human leukocyte antigen DR (HLA-DR), OX40 ligand, CD80, and CD86 and have been shown previously to have antigen-presenting capabilities similar to certain DC subsets. [22][23][24] Activated NK cells can also express CD4 on their surface, 25,26 a molecule typically found on a subset of CD3 ϩ T cells and monocytes/macrophages; however, CD4 has also been observed on many activated cell types including CD8 ϩ T cells, 27 B cells, 28 monocytes, 29 eosinophils, 30 and neutrophils. 31 Given the small percentage of circulating CD4 ϩ NK cells, previous studies have used in vitro stimulation protocols to expand the number of NK cells expressing CD4 25,26 ; however, these activated CD4 ϩ NK cells may not be representative of CD4 ϩ NK cells in vivo.…”

Section: Introductionmentioning

confidence: 99%