BCR/ABL kinase-positive chronic myelogenous leukemia

Vaccines designed to control chronic infections by intracellular agents such as human immunodeficiency virus type 1 (HIV-1) require the induction of cell-mediated immune responses to rid the host of pathogeninfected cells. Listeria monocytogenes has characteristics that make it an attractive vaccine vector for use against such infections. Here we show that parenteral immunization with a new highly attenuated strain of this organism provided complete protection against systemic and mucosal challenges with a recombinant vaccinia virus expressing HIV-1 gag. Immunization also generated a strong, long-term memory cytotoxic-T-lymphocyte (CTL) response in spleen, mesenteric lymph nodes, and Peyer's patches directed against the gag protein. Oral immunization with this attenuated strain also produced complete, long-lasting protection against the recombinant virus but only against mucosal virus challenge. Curiously, oral immunization was associated with a transient CTL response in the three lymphoid tissues examined.

CD8+ T cells are a major component of the adaptive response of a host to infections by viruses and other intracellular pathogenic agents. However, because of the intrinsic immaturity of the immune system of neonatal animals, neonates are highly sensitive to a variety of pathogens and may be unable to respond in a protective manner. Here we explore whether a hyperattenuated strain of Listeria monocytogenes that can be used as a live vaccine vector in adults is safe and able to induce an effective response in neonates. We answer both questions affirmatively

SUMMARYThe goal of vaccination is the generation of immune memory, an immune state that permits rapid and intense recall responses to a pathogen. Considerable effort is being made to understand the nature of memory T cells. We report here that by extending the length of in vitro culture following a single restimulation with speci®c peptide, preparations of highly enriched, highly active antigenspeci®c CD8 memory T cells could be obtained. These cultures were begun with splenocytes from mice primed by infection either with an attenuated strain of Listeria monocytogenes or vaccinia virus, both expressing the human immunode®ciency virus-1-gag gene. In the cultures, antigenspeci®c cytotoxic T lymphocyte (CTL) activity reached a maximum at about 9 days and thereafter fell to negligible values. Concomitant with the fall of CTL activity, however, we observed enrichment for a subset of CD11a high antigen-speci®c gag-tetramer pos CD8 T cells. The cells showed little or no 4-hr CTL activity, but had high delayed (18-hr) CTL activity, and very high cytolytic activity after restimulation. They rapidly expressed interferon-g production. Their growth and survival after sorting was completely dependent on interleukin-2 or -15. As few as 5000 of thē uorescence-activated cell sorting-puri®ed cells protected recipients against challenge 3 months after transfer. In response to the challenge, the cells repopulated lymphoid and non-lymphoid organs and showed a sizeable increase in number. The cells therefore demonstrate high protective activity for long periods of time. These cultured cells are thus a potential source of enriched natural memory T cells for reperfusion studies and in which the mechanisms that underlie the generation, differentiation and persistence of memory can be examined.

Supplementary Figure 3 from BCR/ABL Inhibits Mismatch Repair to Protect from Apoptosis and Induce Point Mutations