The genomic rearrangements in mutant variants of leukemia were studied with the use of genomic HLA typing, microsatellite mapping, and single-nucleotide-polymorphism arrays. The post-transplantation immune responses against the original cells and the mutated leukemic cells were analyzed with the use of mixed lymphocyte cultures.
Results: In 5 of 17 patients with leukemia Bindarit chemical structure relapse after haploidentical transplantation and infusion of donor T cells, we identified mutant variants of the original leukemic cells. In
the mutant leukemic cells, the HLA haplotype that differed from the donor’s haplotype had been lost because of acquired uniparental disomy of chromosome 6p. T cells from the donor and the patient after transplantation did not recognize the mutant leukemic cells, MRT67307 cost whereas the original leukemic cells taken at the time of diagnosis were efficiently recognized and killed.
Conclusions: After transplantation of haploidentical
hematopoietic stem cells and infusion of donor T cells, leukemic cells can escape from the donor’s antileukemic T cells through the loss of the mismatched HLA haplotype. This event leads to relapse.
N Engl J Med 2009;361:478-88.”
“The role of T-lymphocyte subsets in recovery from foot-and-mouth disease virus ( FMDV) infection in calves was investigated by administering subset-specific monoclonal antibodies. The depletion of circulating CD4(+) or WC1(+) gamma delta T cells was achieved for a period extending from before challenge to after resolution of viremia and peak clinical signs, whereas CD8(+) cell depletion was
only partial. The depletion of CD4(+) cells was also confirmed by analysis of lymph node biopsy specimens 5 days postchallenge. Depletion with anti-WC1 and anti-CD8 antibodies had no effect on the kinetics of infection, clinical signs, and immune responses following FMDV infection. Three of the four CD4(+) T-cell-depleted calves failed to generate an antibody response to the nonstructural polyprotein 3ABC but generated a neutralizing antibody response similar to that in the controls, including rapid isotype switching to immunoglobulin G antibody. We conclude that antibody responses to sites on the surface of the virus LY3023414 manufacturer capsid are T cell independent, whereas those directed against the nonstructural proteins are T cell dependent. CD4 depletion was found to substantially inhibit antibody responses to the G-H peptide loop VP135-156 on the viral capsid, indicating that responses to this particular site, which has a more mobile structure than other neutralizing sites on the virus capsid, are T cell dependent. The depletion of CD4(+) T cells had no adverse effect on the magnitude or duration of clinical signs or clearance of virus from the circulation.