scholarly journals Induction of abortion in mice with a monoclonal antibody specific for suppressor T-lymphocyte molecules

Reproduction ◽  
1988 ◽  
Vol 82 (2) ◽  
pp. 691-696 ◽  
Author(s):  
K. D. Beaman ◽  
R. C. Hoversland
1982 ◽  
Vol 101 (3) ◽  
pp. 354-358 ◽  
Author(s):  
Bengt Hallengren ◽  
Arne Forsgren

Abstract. To explore suppressor T lymphocyte function in Graves' disease, studies were performed in one group of patients in the hyperthyroid state and in another group in the euthyroid state after treatment. Peripheral blood lymphocytes were cultured for 1–7 days., Pokeweed mitogen (PWM; 1.25 μg/ml) was added at the initiation of the cultures or after 24 h. The degree of lymphocyte activation was assessed by measurements of the cellular uptake of [3H]thymidine and expressed in counts per minute (cpm). The suppressor lymphocyte function was estimated by a quotient between the maximum cpm values from cultures with and without pre-incubation. For the hyperthyroid group (n = 15) the quotient was 1.00 ± 0.07 (mean ± sem), for the euthyroid patient group (n = 21) 1.12 ± 0.05 and for the healthy control group (n = 21) 1.37 ± 0.08. There was a significant difference between the quotients for the control group and the hyperthyroid (P < 0.01) as well as the euthyroid (P < 0.05) patient group. The quotients for the two groups of patients did not differ significantly. In conclusion, the present study supports the view of a defect in suppressor T lymphocyte function in patients with Graves' disease in the hyperthyroid state and indicates that this defect can persist in the euthyroid state after treatment.


1983 ◽  
Vol 18 (1) ◽  
pp. 61-71 ◽  
Author(s):  
JACQUES HOW ◽  
DUNCAN J. TOPLISS ◽  
CHRISTOPHER STRAKOSCH ◽  
MARK LEWIS ◽  
VAS V. ROW ◽  
...  

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 960-964 ◽  
Author(s):  
JP Daley ◽  
MK Rozans ◽  
BR Smith ◽  
SJ Burakoff ◽  
JM Rappeport ◽  
...  

Abstract We have studied the effect of removing donor T cells by treatment with the monoclonal antibody Leu-1 and complement before marrow transplantation on the regeneration of functionally competent T lymphocytes in the blood at selected times after transplant. Using sensitive limiting-dilution methods that allow us to enumerate helper, cytotoxic, and proliferating T lymphocyte precursors, we report that regeneration of a functional T cell compartment is more severely impaired for the first 180 days after transplantation in those patients given T cell-depleted bone marrow than in recipients of untreated marrow. After this first 6 months, however, patients given T cell- depleted bone marrow had blood T cell frequencies comparable to those observed in patients given untreated marrow. Diminished frequencies of reactive T cells in recipients of depleted marrow could leave them more susceptible to infection or to the recurrence of neoplastic cells.


1982 ◽  
Vol 10 (2) ◽  
pp. 101-102 ◽  
Author(s):  
JEAN M. KANELLOPOULOS ◽  
PETER C. L. BEVERLEY ◽  
ED ZANDERS ◽  
MICHAEL J. CRUMPTON

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13515-13515
Author(s):  
A. Sharma ◽  
P. Bumerts ◽  
J. Gomez-Navarro ◽  
D. Pavlov ◽  
A. Ribas

13515 Background: CP-675,206 is a fully human, cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blocking mAb with immune stimulating properties under development for the treatment of metastatic melanoma. The pharmacokinetics of CP-675,206 is similar to endogenous IgG, with a long plasma half-life (22 days). We explored the use of TPE in two patients (pts) receiving CP-675,206, postulating that TPE could be used to remove mAb in cases where toxicities are thought to result from persistence of mAb in circulation. Methods: For both pts, five TPEs were performed over 7 days using a Cobe Spectra blood cell separator (TPE daily x 3, 2 days rest, and TPE daily x 2). One plasma volume was processed per TPE and replaced with a 60%/40% albumin/saline solution. Plasma CP-675,206 concentration was measured at baseline and after the 3rd and 5th TPE. Results: Patient 1 was a 62 year-old with metastatic melanoma who received 8 monthly doses of CP-675,206 (10 mg/kg). Six days after the last dose, the pt was found to have elevated ALT and bilirubin and detectable anti- smooth muscle and anti-microsomal antibodies. Based on a suspicion of therapy-related autoimmune hepatitis, the pt underwent TPE. Plasma CP-675,206 concentration declined by 96% following the 5th TPE, and ALT and bilirubin normalized over the 4 weeks following TPE with no other evidence of clinical hepatitis. Patient 2 was a 78 year-old with in-transit melanoma who received 3 monthly doses of CP-675,206 (10 mg/kg) and was responding to therapy. Two weeks after the last dose the pt developed diffuse bilateral arthralgias. The pt was diagnosed with rheumatoid factor-negative rheumatoid arthritis, presumably related to therapy with CP-675,206, and underwent TPE. Pre- and post-TPE plasma CP-675,206 concentrations are pending. The arthralgias persisted, and the pt subsequently received oral methotrexate with slow improvement in symptoms over the next 6 months. Conclusions: TPE is highly effective for reducing the plasma concentration of CP-675,206 and may be useful to avert the progression of drug-related adverse events. Clinical benefit from TPE may vary depending on the interval from dosing and may be limited by slow reversibility of T-cell immunostimulation. [Table: see text]


2005 ◽  
Vol 79 (19) ◽  
pp. 12264-12272 ◽  
Author(s):  
Richard Stebbings ◽  
Neil Berry ◽  
Herman Waldmann ◽  
Pru Bird ◽  
Geoff Hale ◽  
...  

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.


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