CD28 Fails to Costimulate Tumor-Specific Activation of Epstein Barr-Virus-Specific Memory Effector T Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1294-1294
Author(s):  
Bianca Altvater ◽  
Sibylle Pscherer ◽  
Heribert Juergens ◽  
Claudia Rossig
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Surface Expression ◽  
Effector T Cells ◽  
Effector Memory ◽  
Cytotoxic T Cell ◽  
Barr Virus ◽  
Epstein Barr ◽  
Signaling Domains

Abstract Genetic modification of cytotoxic T cells with tumor antigen-specific chimeric receptors (chRec) specifically redirects their effector functions towards tumor cells. Integration of the signaling domains of the costimulatory molecule CD28 into chRec enhances antigen-specific proliferation of peripheral blood-derived polyclonal human T cell populations. While CD28 plays an essential role in the priming of naïve CD4+ T cells, its contribution to effector memory cytotoxic T cell (CTL) responses is controversial. We investigated the function of chRec containing the signaling domains of CD28 in vitro expanded T cells with specificity for Epstein-Barr-virus (EBV). Chimeric T cell receptors containing an extracellular single-chain antibody domain directed against the tumor ganglioside antigen GD2 fused to the intracellular signaling domains of both the CD28 and the T cell receptor (TCR) ζ chain (14.G2a-CD28ζ), or TCRζ alone (14.G2a-ζ) were expressed in EBV-specific cytotoxic T cell (CTL) lines from three seropositive donors and in peripheral blood T cells preactivated by CD3-/CD28-specific antibody crosslinking by retroviral gene transfer. Following transduction with the chRec genes, 14.G2a-ζ and 14.G2a-CD28ζ EBV-CTL had comparable levels of chRec surface expression (21–28% versus 26–40%). EBV-CTL had an immunophenotype characteristic of memory effector T cells, coexpressing CD3 and CD45RO in the absence of CD45RA and CD27 surface expression. The transduced CTL maintained their capacity to specifically lyse autologous EBV targets in 4 hr 51Cr release assays and to proliferate after stimulation with autologous EBV targets. Intracellular cytokine staining demonstrated efficient and comparable antigen-specific IFN-γ secretion by both 14.G2a-ζ and 14.G2a-CD28ζ-transduced CTL in response to EBV and tumor targets. Furthermore, GD2+ neuroblastoma targets were lysed in a comparable and antigen-specific manner. However, while antigen engagement by 14.G2a-CD28ζ efficiently induced expansion of non-specifically activated polyclonal peripheral blood lymphocytes in an antigen-dependent manner, CD28 signaling failed to overcome the failure of transduced EBV-CTL to specifically proliferate in response to GD2+ tumor cells. Thus, the costimulatory requirement for the highly efficient proliferative activation response of EBV-specific CTL to viral antigen can not be mimicked by combined CD28 and ζ signaling. Exploring the mechanisms and costimulatory requirements of effector memory T cell reactivation may help to exploit the full potential of this highly cytolytic T cell population for adoptive immunotherapy of cancer.

scholarly journals Deficiency of CD8+ effector memory T cells is an early and persistent feature of multiple sclerosis

2014 ◽  
Vol 20 (14) ◽  
pp. 1825-1832 ◽  
Author(s):  
Michael P Pender ◽  
Peter A Csurhes ◽  
Casey MM Pfluger ◽  
Scott R Burrows
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Clinical Course ◽  
Effector Memory ◽  
Barr Virus ◽  
Effector Memory T Cells ◽  
The Central Nervous System ◽  
Epstein Barr

Background: Patients with multiple sclerosis (MS) have a deficiency of circulating CD8+ T cells, which might impair control of Epstein–Barr virus (EBV) and predispose to MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. Based on the expression of CD45RA and CD62L, CD4+ T cells and CD8+ T cells can be subdivided into four subsets with distinct homing and functional properties, namely: naïve, central memory, effector memory (EM) and effector memory re-expressing CD45RA (EMRA) cells. Objective: Our aim was to determine which memory subsets are involved in the CD8+ T cell deficiency and how these relate to clinical course. Methods: We used flow cytometry to analyze the memory phenotypes of T cells in the blood of 118 MS patients and 112 healthy subjects. Results: MS patients had a decreased frequency of EM (CD45RA–CD62L–) and EMRA (CD45RA+CD62L–) CD8+ T cells, which was present at the onset of disease and persisted throughout the clinical course. The frequencies of CD4+ EM and EMRA T cells were normal. Conclusion: Deficiency of effector memory CD8+ T cells is an early and persistent feature of MS and might underlie the impaired CD8+ T cell control of EBV.

scholarly journals TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells

2020 ◽  
Vol 5 (49) ◽  
pp. eaba7918 ◽  
Author(s):  
Takuya Sekine ◽  
André Perez-Potti ◽  
Son Nguyen ◽  
Jean-Baptiste Gorin ◽  
Vincent H. Wu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Chronic Infections ◽  
Activation Markers ◽  
Barr Virus ◽  
Gene And Protein Expression ◽  
Epigenetic Remodeling ◽  
Epstein Barr

CD8+ T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8+ T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8+ T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8+ T cell landscape. Here, we demonstrate that circulating TOX+ CD8+ T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8+ T cells generally expressed TOX, whereas naive and early-differentiated memory CD8+ T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8+ T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8+ T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8+ T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8+ T cell subsets and not exclusively linked to exhaustion.

scholarly journals T Cell Exhaustion and Senescence in Epstein-Barr Virus-Associated Lymphoma Patients

2020 ◽  
Author(s):  
Huihui Liu ◽  
Junhui Xu ◽  
Lihong Wang ◽  
Wenjun Mao ◽  
Bingjie Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Barr Virus ◽  
Cell Counts ◽  
Healthy Donors ◽  
Epstein Barr

Abstract Background The Epstein-Barr Virus (EBV) is tumorigenic, and can be detected in many kinds of lymphomas. Some studies have shown a worse prognosis for patients with EBV-associated lymphoma. However, the mechanism is not fully understood. This study aimed to investigate the T cell signatures in patients with EBV-associated lymphoma. Methods Peripheral blood was collected from 17 patients with EBV-associated lymphoma and 19 healthy donors. We first examined the proportions of the lymphocyte subpopulations in peripheral blood mononuclear cells in patients with both groups by flow cytometry. Then we employed the enzyme-linked immunospot assay to evaluate the EBV antigen-specific response of the cytotoxic T cells in the two groups. Finally, to explore the mechanism of T cells dysfunction in EBV-associated lymphoma, we examined the expression of multiple inhibitory receptors representing T cell exhaustion and biomarkers representing T cell senescence on the surfaces of CD4+ T cells and CD8+ T cells. Results The ratio of peripheral CD4+ T cells and the absolute cell counts of CD4+ T cells and CD8+ T cells were significantly decreased in patients with EBV-associated lymphoma compared with those of healthy donors. The IFN-γ production upon stimulation of EBV mixed peptides were remarkably reduced in the patients. Higher expression levels of T cell exhaustion markers, PD1, LAG3, TIM3 and CTLA4 on T cells were found in the patients. The two subsects of exhausted T cells (T-bethiPD1mid and EOMEShiPD1hi) were higher in the patients. More importantly, CXCR5+CD8+T cells controlling viral replication decreased significantly in the patients. The fractions of senescent T cells increased in the patients. Conclusions In summary, our study demonstrated that the reduced EBV-specific T cells, the exhaustion and senescence of T cells together contributed to the T cell dysfunction in the patients with EBV-associated lymphoma.

Epstein-Barr Virus (EBV) Associated Post-Transplantation Lymphoproliferative Disorder Confined to the Central Nervous System Despite Negative Serum EBV PCR Following Rituxmab Administration.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4303-4303
Author(s):  
Cannon Milani ◽  
Rami Abumasmah ◽  
Ahmad-Samer Al-Homsi
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Cytotoxic T Cell ◽  
Quiescent State ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Epstein Barr

Abstract Abstract 4303 Post-Transplant Lymphoproliferative Disorders (PTLD) represents a wide spectrum of clinical disorders complicating immunosuppressive regimens in transplant recipients. The development of PTLD is linked to a deficient Epstein-Barr Virus (EBV) specific cellular immune response. In association with allogeneic stem-cell transplantation (SCT), PTLD has been considered a rare entity (incidence ≤ 1 percent). However risk factors such as HLA disparity, in vitro or in vivo T-cell depletion, and severe Graft Versus Host Disease (GVHD) confer an increased risk. According to several observational historical studies on PTLD after SCT, CNS involvement in disseminated PTLD occurred in up to 28.6% of cases and was associated with poor prognosis. On the other hand, isolated EBV-related CNS PTLD, is exceedingly rare. In immunocompetent individuals, EBV immortalizes infected lymphocytes, but is kept in a quiescent state through the cytotoxic T-cell response. Without the benefit of a healthy immune system, EBV-infected lymphocytes may proliferate unchecked and lead to PTLD lesions. PCR technology has recently been used to monitor EBV load in high-risk patients following organ or marrow transplantation. Real-time PCR is a rapid and reproducible method for quantifying DNA that was first introduced for EBV in 1999. Studies have demonstrated that EBV-driven PTLD is almost always accompanied by an increase in the level of circulating EBV DNA within the peripheral blood. These findings have led to the development of programs that monitor peripheral blood viral load in the post-transplant period by quantitative PCR. Such monitoring programs are noninvasive and have demonstrated success in detecting PTLD in its earliest stages. In many cases, early detection allows clinicians to treat by adjusting immunosuppressive regimens, rather than introducing cytotoxic chemotherapy in advanced lesions. More recently, clinicians have started relying on Rituximab to treat EBV reactivation. The discovery of an EBV-driven CNS PTLD in our patient is unusual in that there was no evidence of EBV in the peripheral blood by PCR. Two similar cases have been reported in the literature. The nature of this phenomenon is uncertain. One plausible explanation is the effectiveness of Rituximab in clearing the virus from the peripheral blood but not from the CNS, given its poor blood-brain barrier penetration. If this was the case, one might fear an increase in the CNS localization of PTLD as clinicians increasingly rely on the use of Rituximab in face of rising EBV viral load in the peripheral blood. In summation, we believe that clinicians should be aware of the potential possibility of CNS PTLD in the absence of PCR-evidence of EBV reactivation in the peripheral blood in patients treated with Rituximab. Efforts must continue to develop alternative approaches to preemptive treatments of EBV re-activation such as with adoptive immunotherapy. Disclosures: No relevant conflicts of interest to declare.

Signaling Domain of Chimeric Antigen Receptors Can Reprogram T Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 551-551
Author(s):  
Omkar Uday Kawalekar ◽  
Roddy O'Connor ◽  
Sonia Guedan ◽  
Joseph Fraietta ◽  
Avery D. Posey ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Intracellular Signaling ◽  
Research Funding ◽  
Effector Memory ◽  
Car T Cells ◽  
Car T ◽  
Signaling Domains

Abstract BACKGROUND Chimeric antigen receptors (CARs) redirect T cells to recognize tumor cells, providing a powerful new approach to cancer immunotherapy. However, the attributes of CARs that ensure optimal in vivo tumor destruction and persistence of the CAR remain to be defined. Here, we analyze the influence of the signaling domain on the proliferation and function of CAR T cells. We find that distinct costimulatory domains in the CAR architecture have major effects on cell longevity, memory differentiation, and cell metabolism characteristics. METHODS We developed a novel system of in vitro T cell stimulation to study the consequences of a single round of CAR-specific stimulation in order to analyze signaling through various CAR signaling endodomains. By electroporation of in vitro transcribed mRNA encoding CAR into primary resting human T cells, we achieved >90% CAR- positive T cell population. We expressed anti-mesothelin SS1-CAR constructs with varying intracellular signaling domains (CD3zeta, CD28:z, and 4-1BB:z), all specific for a widely expressed tumor-associated antigen, mesothelin. Upon verifying CAR expression, these T cells were stimulated with recombinant mesothelin immobilized on beads and then cultured. With only a transient expression of CARs, the CAR disappears from the surface after one round of stimulation, allowing the unambiguous analysis of signaling through the CAR alone. This approach thus obviated the requirement for stimulation through the endogenous T cell receptor and permitted for the first time, an analysis of the consequences of signaling through the surrogate antigen of CAR T cells. Experiments were conducted on primary peripheral blood T cells, sorted naïve T cells and cord blood T cells. RESULTS To examine whether intracellular signaling domains influence the in vitro function and antitumor activity of CAR-T cells, we developed a new culture system that permits rapid screening of novel CAR designs. The various CAR constructs demonstrated comparable and specific cytolytic capabilities when cultured with target cells that expressed mesothelin. However, primary T cells stimulated through the 4-1BBz-containing CARs showed superior survival and expansion profiles when compared to CD28-based CARs. Phenotypic analysis of 4-1BB-based CAR T cells revealed that an increased population of cells with central-memory surface markers was generated. On the other hand, cells endowed with CD28z-containing CARs yielded a significantly higher proportion of effector memory cells, with a modest increase in expression of inhibitory PD-1, TIM3 and LAG3 molecules relative to their 4-1BBz counterparts. These results remained consistent whether starting populations of bulk peripheral blood T cells, naïve (CD45RO-CD95- CD62L+CCR7+ sorted) peripheral blood T cells, or cord blood T cells were used. Metabolic profiling of the mesothelin-stimulated cells CAR T cells by the Sea-Horse assay in culture revealed a substantial increase in lipid oxidation in 4-1BBz-CAR stimulated cells compared to their 28z counterpart. Additionally, microarray studies have revealed a unique gene signature in cells that are recovered after stimulation through the different CAR signaling domains. CONCLUSIONS We report the development of a novel system to study signal transduction in primary T cells after stimulation through their surrogate antigen. Following the initial stimulation of CAR T cells by the surrogate antigen mesothelin, both 4-1BB and CD28-based CARs had a burst of more than 5 population doublings. However, the 4-1BB CAR T cells proliferated for longer in vitro. In addition to quantitative differences in proliferation, there were qualitative differences that emerged as a function of the signaling endodomain. 4-1BB-based CAR T cells displayed features of central memory T cells, while CD28-based CARs T cells rapidly differentiated to an effector memory pool of CAR T cells. Other differences between 4-1BB and CD28-based CARs were uncovered, including differential expression of inhibitory checkpoint molecules, metabolic reprogramming, and gene signatures. Together these results may explain the differential survival reported with CD28 and 4-1BB based CAR T cells in clinical trials, and inform the development of CARs with novel signaling domains. These results also provide a new system to rapidly evaluate new CAR designs. Disclosures Scholler: Novartis: Research Funding. Milone:Novartis: Research Funding. June:Novartis: IP licensed by University of Pennsylvania to Novartis. Author entitled to royalties from the University. Patents & Royalties, Research Funding.

Infusion Of Donor-Derived CD19-Redirected-Virus-Specific T Cells For B-Cell Malignancies Relapsed After Allogeneic Stem Cell Transplant: A Phase I Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 152-152 ◽  
Author(s):  
Conrad Russell Y. Cruz ◽  
Kenneth P. Micklethwaite ◽  
Barbara Savoldo ◽  
Carlos A. Ramos ◽  
Sharon Lam ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Research Funding ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr ◽  
Relapsed Disease ◽  
Anti Tumor Activity

Abstract Donor lymphocyte infusions (DLI) following hematopoietic stem cell transplantation may reduce or control opportunistic infections and leukemia/lymphoma relapse, but the associated graft versus host disease (GvHD) limits the clinical success of this procedure. Since T cell immunotherapy may be a safer alternative to DLI we have now used a single T cell platform that mediates both antileukemic and antiviral activity. Autologous T cells modified to express CD19-specific chimeric antigen receptors (CD19.CAR) have had clinical activity against CD19-expressing malignancies, but it is unknown if similarly modified allogeneic T cells will be equally effective. Allogeneic virus specific T cells (VSTs) directed to cytomegalovirus (CMV), adenovirus (Adv), and Epstein Barr virus (EBV) have been shown to be safe and effective in preventing and treating life-threatening viral infections post HSCT. Therefore, we sought to determine whether allogeneic VSTs could be engineered to express CD19.CAR and would retain the safety and effectiveness of unmodified VSTs whilst gaining anti-tumor activity. VSTs were expanded ex vivo using antigen presenting cells engineered to express adenovirus and cytomegalovirus (using an Ad5f35 adenoviral vector expressing the CMV pp65 gene), and Epstein Barr virus (using EBV-infected lymphoblastoid cell lines) antigens. After 3 stimulations, the VST’s were modified to express CD19.CAR.28ζ using a retroviral vector encoding the CAR-CD19 receptor coupled to the CD28 co-stimulatory molecule and the T cell receptor zeta (ζ) chain. Nine CD19.CAR-modified virus specific T cell (CD19.CAR-VSTs) products were generated for infusion. All VST lines recognized at least one viral antigen as determined by Elispot or chromium release assays and 20% to 48% of cells expressed the CD19.CAR. All lines killed CD19-expressing cells in vitro. We treated nine patients with these CD19.CAR-VSTs, 3 months to 13 years after HSCT. Six patients received CD19.CAR-VSTs for relapsed disease and 3 patients received the T cells as adjuvant therapy to prevent viral infection and relapse after HSCT. Safety. There were no infusion-related toxicities. One patient presented with gastrointestinal symptoms following infusion subsequently determined to be unrelated to the T cells. Persistence. VSTs persisted a median of 8 weeks in the peripheral blood and up to 9 weeks at disease sites. In three patients (#1, #3 and #5), CD19.CAR signals were detectable in the bone marrow or the lymph nodes (44.8, 25.85, and 32 copies/1000 ng DNA) even when no signal was measurable in peripheral blood, indicating preferential accumulation of the infused T cells at the disease site. Anti-Tumor Activity. During the period of CD19.CAR-VST persistence, objective anti-tumor activity was evident in 2/6 patients with relapsed disease (patient # 1 had detectable blasts in the peripheral blood which disappeared within 1-2 weeks following infusion, patient # 2 had 16% circulating CLL cells which decreased within 2 weeks of T cell infusion) but disease recurred after 3 and 2 months, respectively. The two patients who received cells while in remission remain disease-free >3 and >9 months later. Anti-Viral Activity. In two patients with EBV reactivation, donor CD19.CAR-VSTs expanded concomitant with an increase in virus-specific T cell responses, and decreased viral load. A third patient had a rise in adenovirus specific VSTs during an episode of adenovirus associated diarrhea. Although the infection was controlled, there was no concomitant rise in CD19-CAR expressing T cells in this patient. No other patient had viral disease. In conclusion, allogeneic CD19.CAR-VSTs administered after allogeneic HSCT are safe and can exert both anti-tumor and anti-viral activity in the absence of GvHD. Earlier administration of CD19.CAR-VSTs after HSCT, when the host is lymphodepleted and the incidence of viral infection is higher, may allow these cells to better capture the potential advantages of native TCR stimulation (and associated co-stimulation) for expansion and persistence, and thereby produce a higher frequency of sustained tumor responses. Alternatively, intentional stimulation of the native TCRs by viral vaccines may produce equal benefit, with greater predictability. Disclosures: Savoldo: Celgene: Patents & Royalties, Research Funding. Heslop:Celgene: Patents & Royalties, Research Funding; Cell Medica: Patents & Royalties. Rooney:Cell Medica: Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties, Research Funding; Celgene: Patents & Royalties, Research Funding. Brenner:Celgene: Patents & Royalties, Research Funding. Dotti:Celgene: Patents & Royalties, Research Funding.

Quantitation, selection, and functional characterization of Epstein-Barr virus–specific and alloreactive T cells detected by intracellular interferon-γ production and growth of cytotoxic precursors

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1730-1740 ◽  
Author(s):  
Guenther Koehne ◽  
Katherine M. Smith ◽  
Teresa L. Ferguson ◽  
Roxanne Y. Williams ◽  
Glenn Heller ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Flow Cytometric Analysis ◽  
Interferon Γ ◽  
Cytotoxic T Cell ◽  
Barr Virus ◽  
Alloreactive T Cells ◽  
Ifn Γ ◽  
Epstein Barr

Techniques for the quantitation of virus-specific and alloantigen-reactive T cells vary in their measurement of clinically relevant T-cell effector populations, their sensitivity and quantitative accuracy, and the time required to obtain measurable results. We compared frequencies of Epstein-Barr virus (EBV)–specific and major alloantigen-reactive T cells as measured by flow cytometric analysis of responding T cells producing intracellular interferon-γ (IFN-γ) and by limiting-dilution analysis (LDA) of cytotoxic T-cell precursors (CTLp) at sequential time points during the generation of EBV-specific T-cell lines. The expansion of EBV-specific T lymphocytes and the depletion of alloreactive T cells in cultures of T cells sensitized with autologous EBV-transformed targets followed similar kinetics when measured by either method. Frequencies of EBV- specific T cells generating intracellular IFN-γ exceeded by 25- to 90-fold the frequencies of responding CTLp at each stage of expansion, whereas the frequencies of alloreactive T cells generating intracellular IFN-γ exceeded by 30- to 220-fold those detected by LDA. The assay that quantitated T cells producing IFN-γ yielded more reproducible and precise results than LDA. Furthermore, frequencies detected by the enumeration of T cells responding to immunodominant EBNA 3a and EBNA 3c peptides by IFN-γ production or their capacity to bind peptide-HLA tetramers were strikingly similar and represented significant fractions of T cells generating IFN-γ in response to autologous EBV B lymphoblastoid cell line. Functional analysis of responding viable T cells, fractionated on the basis of their secretion of IFN-γ, demonstrated that EBV-specific and alloantigen cytotoxic T cells were predominately or exclusively detected in the CD8+IFN-γ+ fraction of T cells. Strikingly, the CD4+IFN-γ+ cell fractions were not cytotoxic against EBV-transformed or allogeneic targets.

scholarly journals Helper cell-independent cytotoxic clones in man.

1982 ◽  
Vol 156 (6) ◽  
pp. 1854-1859 ◽  
Author(s):  
S L Wee ◽  
L K Chen ◽  
G Strassmann ◽  
F H Bach
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Helper Cell ◽  
Cytotoxic T Cell ◽  
Lymphoblastoid Cell Lines ◽  
Barr Virus ◽  
Mediate Cytotoxicity ◽  
Epstein Barr ◽  
And Function

We report here a class of helper cell-independent cytotoxic T cell (HITc) clones in man that can proliferate in response to antigenic stimulation as well as mediate cytotoxicity. HITc appear to be rare among clones derived from primary in vitro allosensitized culture, but constitute the majority of clones derived from cells sensitized to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines. The implications of the derivation and function of HITc clones are discussed.

Sign in / Sign up

Export Citation Format

Share Document