Culturing of human peripheral blood cells reveals unsuspected lymphocyte responses relevant to HIV disease

Sahaf, Bita; Atkuri, Kondala R.; Heydari, Kartoosh; Malipatlolla, Meena; Rappaport, Jay; Régulier, Emmanuel G.; Herzenberg, Leonard A.; Herzenberg, Leonore A.

doi:10.1073/pnas.0712363105

Cited by 34 publications

(25 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5,6 In time, the innate immune system production of pro-inflammatory activating cytokines subsides, leaving Tat protein to maintain the chronic activated state of the adaptive immune system and the set point HIV viremia characteristic of chronic HIV infection.…”

Section: Resultsmentioning

confidence: 99%

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

Goldstein

Damiano

Donikyan

et al. 2012

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

Goldstein

Damiano

Donikyan

et al. 2012

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…IL-2 (50 IU/mL) and BAFF (R&D Systems) were tested at 10 ng/mL. Cultures were maintained at 37°C with 5% CO 2 in 5% O 2 incubators (27). Harvested supernatant was stored at −80°C before IgG ELISAs.…”

Section: Methodsmentioning

confidence: 99%

H–Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease

Sahaf¹,

Yang

Arai³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

B cells are known to play an important role in pathogenesis of human chronic graft vs. host disease (cGVHD). Our group has previously shown that IgG allo-antibodies recognize Y chromosomeencoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 mo after transplant in male patients who receive grafts from female donors (F→M) hematopoietic cell transplantation (HCT). Here we present FACS studies of peripheral blood mononuclear cells collected 6 mo after transplant showing that 16 of 28 (57%) F→M HCT patients have circulating donor B cells that express B-cell receptor (mainly IgM and Igλ) specific for DBY-2. The detection of these DBY-2 B cells 6 mo after HCT are associated with cGVHD development (P = 0.004). Specifically, 15 of 16 F→M with DBY-2 B cells developed cGVHD. In contrast, cGVHD developed in only 5 of the 12 who did not have DBY-2 B cells detected. This demonstrates circulating human B cells binding an alloantigen (DBY-2) and that these DBY-2-specific B cells appear before development of cGVHD in roughly half of the F→M patients. Our study suggests that detection of anti-DBY-2 B cells may predict cGVHD and that this prediction may have clinical utility. Validation of this hypothesis will require larger prospective studies.allogeneic | antigen-specific B cells | transplantation | DDX3Y

show abstract

“…16,17 Immune phenotype analysis Multiparameter flow cytometric analysis was carried out with cell staining methods as described previously. 18,19 After thawing cryopreserved peripheral blood mononuclear cell (PBMC) samples, cell suspensions were tested with the LIVE/DEAD kit (Life Technologies, San Diego, CA) with at least 85% viability after thawing. Cells were then washed and stained for 15 minutes with mixtures of fluorochrome-conjugated antibodies against cell-surface marker proteins, including CD3, CD4, CD5, CD8, CD19, CD23, CD24, CD25, CD27, CD38, CD45, CD45RA, CD45RO, CD62L, CCR7, CD127, CXCR5 (CD185), IgD, IgM, Va24, and CD230.…”

Section: Mrd Monitoring and Donor Chimerism Assessmentmentioning

confidence: 99%

Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT

Ryan

Sahaf

Logan

et al. 2016

Blood

Self Cite

View full text Add to dashboard Cite

• Ibrutinib provided effective salvage therapy in CLL relapse post-alloHCT, resulting in sustained MRD negativity without GVHD development.• Ibrutinib selectively depleted pre-germinal B cells and Th2 helper cells and may enhance donor Th1 T-cell-mediated GVL effects.Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton's tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87.5%. An additional 11 patients were treated at Stanford University following US Food and Drug Administration approval of ibrutinib; 7 (64%) achieved a complete response, and 3 (27%) achieved a partial response. Of the 9 patients treated at Stanford who had mixed chimerism-associated CLL relapse, 4 (44%) converted to full donor chimerism following ibrutinib initiation, in association with disease response. Four of 11 (36%) patients evaluated by ClonoSeq achieved minimal residual disease negativity with CLL <1/10 000 white blood cells, which persisted even after ibrutinib was discontinued, in 1 case even after 26 months. None of the 27 patients developed graft-versus-host-disease (GVHD) following ibrutinib initiation. We postulate that ibrutinib augments the graft-versus-leukemia (GVL) benefit through a T-cell-mediated effect, most likely due to ITK inhibition. To investigate the immune modulatory effects of ibrutinib, we completed comprehensive immune phenotype characterization of peripheral B and T cells from treated patients. Our results show that ibrutinib selectively targets pre-germinal B cells and depletes Th2 helper cells. Furthermore, these effects persisted after drug discontinuation. In total, our results provide evidence that ibrutinib effectively augments GVL without causing GVHD. (Blood. 2016;128(25):2899-2908

show abstract

Culturing of human peripheral blood cells reveals unsuspected lymphocyte responses relevant to HIV disease

Cited by 34 publications

References 29 publications

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation

H–Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease

Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT

Contact Info

Product

Resources

About