C1.7 MONOCLONAL ANTIBODY DESIGNATES HIGH-AVIDITY CD4+ CYTOTOXIC T LYMPHOCYTES INVOLVED IN CLINICAL HEART REJECTION

1998 ◽  
Vol 66 (1) ◽  
pp. 135-138 ◽  
Author(s):  
Nancy E.M. van Emmerik ◽  
Christiaan J. Knoop ◽  
Leonard M.B. Vaessen ◽  
Aggie H.M.M. Balk ◽  
Bas Mochtar ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
High Avidity

scholarly journals CD8+ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

2005 ◽  
Vol 79 (19) ◽  
pp. 12264-12272 ◽  
Author(s):  
Richard Stebbings ◽  
Neil Berry ◽  
Herman Waldmann ◽  
Pru Bird ◽  
Geoff Hale ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphoid Tissue ◽  
Human Immunoglobulin ◽  
Wild Type ◽  
Lymphocyte Depletion ◽  
Immunodeficiency Virus

ABSTRACT In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

Bispecific Monoclonal Antibody Targeted Cytotoxic T Lymphocytes can Recycle

T Lymphocytes ◽  
1992 ◽  
pp. 247-249
Author(s):  
J. A. C. Voorthuis ◽  
E. Braakman ◽  
C. P. M. Ronteltap ◽  
N. E. B. A. M. van Esch ◽  
R. L. H. Bolhuis
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Bispecific Monoclonal Antibody

scholarly journals High-avidity cytotoxic T lymphocytes specific for a new PRAME-derived peptide can target leukemic and leukemic-precursor cells

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3353-3362 ◽  
Author(s):  
Concetta Quintarelli ◽  
Gianpietro Dotti ◽  
Sayyeda T. Hasan ◽  
Biagio De Angelis ◽  
Valentina Hoyos ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Progenitor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Hematologic Malignancies ◽  
High Avidity ◽  
Normal Tissues ◽  
Artificial Antigen ◽  
Leukemia Relapse ◽  
Antigen Presenting ◽  
Restricted Epitope

Abstract The cancer testis antigen (CTA) preferentially expressed antigen of melanoma (PRAME) is overexpressed by many hematologic malignancies, but is absent on normal tissues, including hematopoietic progenitor cells, and may therefore be an appropriate candidate for T cell–mediated immunotherapy. Because it is likely that an effective antitumor response will require high-avidity, PRAME-specific cytotoxic T lymphocytes (CTLs), we attempted to generate such CTLs using professional and artificial antigen-presenting cells loaded with a peptide library spanning the entire PRAME protein and consisting of 125 synthetic pentadecapeptides overlapping by 11 amino acids. We successfully generated polyclonal, PRAME-specific CTL lines and elicited high-avidity CTLs, with a high proportion of cells recognizing a previously uninvestigated HLA-A*02–restricted epitope, P435-9mer (NLTHVLYPV). These PRAME-CTLs could be generated both from normal donors and from subjects with PRAME+ hematologic malignancies. The cytotoxic activity of our PRAME-specific CTLs was directed not only against leukemic blasts, but also against leukemic progenitor cells as assessed by colony-forming–inhibition assays, which have been implicated in leukemia relapse. These PRAME-directed CTLs did not affect normal hematopoietic progenitors, indicating that this approach may be of value for immunotherapy of PRAME+ hematologic malignancies.

KINETICS OF CIRCULATING HIGH AVIDITY CYTOTOXIC T LYMPHOCYTES IN PEDIATRIC AND ADULT RECIPIENTS OF CRYOPRESERVED HUMAN HEART VALVE ALLOGRAFTS.

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S185
Author(s):  
Marij J.P. Welters ◽  
Frans B.S. Oei ◽  
Leonard M.B. Vaessen ◽  
Ad J.J.C. Bogers ◽  
Willem Weimar
Keyword(s):  
T Lymphocytes ◽  
Heart Valve ◽  
Cytotoxic T Lymphocytes ◽  
Human Heart ◽  
High Avidity ◽  
Kinetics Of

scholarly journals High avidity cytotoxic T lymphocytes to a foreign antigen are efficiently activated following immunization with a recombinant paramyxovirus, simian virus 5

2002 ◽  
Vol 83 (5) ◽  
pp. 1167-1172 ◽  
Author(s):  
Griffith D. Parks ◽  
Martha A. Alexander-Miller
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Simian Virus ◽  
Effective Vaccine ◽  
High Avidity ◽  
Vaccine Vectors ◽  
Ctl Response ◽  
Foreign Antigen ◽  
Simian Virus 5

Our previous work has shown that high avidity cytotoxic T lymphocytes (CTL) are optimal for virus clearance in vivo and thus it is necessary that an effective vaccine is capable of eliciting high avidity CTL. To determine if vaccination with the paramyxovirus simian virus 5 (SV5) elicits a high avidity response to a model foreign antigen, a recombinant virus was engineered to express chicken ovalbumin (rSV5–Ova). To compare the CTL response elicited with rSV5–Ova and a recombinant vaccinia virus expressing ovalbumin (rVV–Ova), mice were vaccinated intranasally with various doses of each vector and the Ova-specific CTL response was determined by ELISPOT analysis. Here, it has been shown that rSV5 can be equally as effective as rVV in eliciting antigen-specific CTL, in terms of both the total number of CTL and the number of high avidity cells. This has implications for both the design of vaccine vectors and the route utilized for vaccine administration for the elicitation of high avidity CTL responses. The advantages and future potential use of rSV5 vaccine vectors are discussed.

scholarly journals Tolerance to p53 by A2.1-restricted Cytotoxic T Lymphocytes

1997 ◽  
Vol 185 (5) ◽  
pp. 833-842 ◽  
Author(s):  
Matthias Theobald ◽  
Judith Biggs ◽  
Javier Hernández ◽  
Joseph Lustgarten ◽  
Colleen Labadie ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Transgenic Mice ◽  
Cytotoxic T Lymphocytes ◽  
P53 Protein ◽  
High Avidity ◽  
Wild Type ◽  
Major Barrier ◽  
Cell Immunotherapy ◽  
Immunotherapy Of Cancer ◽  
Wild Type P53

Elevated levels of the p53 protein occur in ∼50% of human malignancies, which makes it an excellent target for a broad-spectrum T cell immunotherapy of cancer. A major barrier to the design of p53-specific immunotherapeutics and vaccines, however, is the possibility that T cells may be tolerant of antigens derived from wild-type p53 due to its low level of expression in normal thymus and lymphohemopoetic cells. The combination of p53 deficient (p53−/−) and p53+/+ HLA-A2.1/Kb transgenic mice was used as a model to explore the possibility that A2.1restricted cytotoxic T lymphocytes (CTL) are functionally tolerant of self peptides derived from the wild-type p53 tumor suppressor protein. A2.1-restricted CTL specific for a naturally processed p53 self-epitope spanning residues 187-197 were completely aborted in p53+/+ as opposed to p53−/− transgenic mice. In contrast, CTL specific for a second self-epitope spanning residues 261-269 of the murine p53 sequence were detected in both p53−/− and p53+/+ A2.1/Kb transgenic mice. However, the avidity of the CTL effectors obtained from p53+/+ mice was 10-fold lower than that obtained from p53−/− mice, again suggesting elimination of CTL with high avidity for the A2.1-peptide complex. The circumvention of functional tolerance of high avidity CTL may therefore be a necessary prerequisite for optimizing immunotherapy against A2.1-restricted wild-type p53 epitopes in humans.

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