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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo.
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PMID:Correlation of graft-versus-host mortality and positive CML assay in the mouse. 1 Jun 48

The gene products of the LA and FOUR loci of the human Major Histocompatibility Complex (MHC) are generally considered to be a major target in the Indirect Cell Mediated Lympholysis (ICML) test. Within most experiments, a positive correlation exists between the number of HL-A antigens challenged and lympholysis. When different experiments are collated this correlation is less obvious. This discrepancy might be caused by differences between the individual HL-A antigens involved in the afferent phase (MLC) and/or the efferent phase (CML). In 28 experiments involving 97 unrelated individuals we have compared statistically 12 different antigens governed by the LA and FOUR loci. When only one of these antigens is challenged in ICML, target lymphocytes are lysed to different degrees allowing a significant classification of the antigens into different groups, which do not coincide with the classification in the LA and FOUR series antigens. It is concluded that the antigens of the HL-A system are not of equal importance when challenged separately in ICML. The existence of a separate CML locus and a corresponding linkage disequilibrium to the SD loci of the MHC region is suggested.
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PMID:Cell mediated lympholysis in man. Varying strength of the HL-A (LA and FOUR) antigens as sensitizing or target determinants. 5 5

The role of HLA antigens in the generation of cytotoxic cells in CML has been investigated. Cytotoxic effector cells were generated in MLC among HLA-A or HLA-A and HLA-B disparate, HLA-D identical siblings, and among HLA-A and HLA-B disparate, MLC identical (%RR less than or equal to 2 3.6) unrelated individual. The data indicate that HLA-D differences and poliferative MLC responses as measured by 3H-thymidine incorporation are not requisite for the in vitro generation of cytotoxic cells and suggest the existence of a CML-S locus (loci) distinct from HLA-A, HLA-B and HLA-D. The degree of cytotoxicity generated in a proliferative versus a "nonproliferative" MLC was comparable. In addition, these studies demonstrate that antigens other than the currently definable HLA-A, HLA-B, HLA-C, and HLA-D can serve as target determinants in cell-mediated lympholysis.
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PMID:The genetics of cell-mediated lympholysis. 6 6

MLC-CML reactivity declines after approximately the 7th day of culture. The experiments described were designed to probe the reason for this decline, envisaged as due to the signals (SD or LD determinants) required for CML activation. Either fresh stimulating cells or a lymphokine--blastogenic factor (BF)--were added daily to mixed cultures from the 5th to the 12th day of incubation. Whereas stimulating cells were without effect, added BF maintained both proliferative and cytotoxic activity of the cells in culture. These observations, together with previous results, were interpreted to suggest that helper cells may regulate the activation of cytotoxic lymphocytes by means of soluble mediators.
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PMID:[The regulation of the activation of cytotoxic lymphocytes may be mediated by a lymphokine]. 6 6

Mice made tolerant to allogeneic tissues in neonatal life have been examined at different times for their ability to respond to the tolerizing determinants in a variety of assays (in vitro CML, MCL and in vivo GvH assays). All animals were tolerant in terms of their inability to produce CTL to the relevant determinants, and to induce GvH in lethally irradiated F1 recipients. Nevertheless, some mice also showed a normal MLC proliferative response and contained antigen-specific serum inhibitory factors, while other mice contained apparently antigen-specific suppressor cells. The pool of the latter, futhermore, was expanded considerably upon adoptive transfer of tolerant cells (with tolerizing antigens) to lethally irradiated syngeneic recipients. The data are compatible with the notion that suppression of clonal expansion represents the primary mechanism of tolerance maintenance (induction), and that the infrequently observed serum reactivity in such tolerant mice represents a vestige of the means whereby-cell mediated suppression was induced.
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PMID:Analysis of mechanisms of maintenance of neonatally induced tolerance to foreign alloantigens. 8 23

Lymphocytes from a healthy female repeatedly giving rise to MLC-typing response against HLA--D homozygous typing cells of three different specificities were investigated for cytotoxic capacity by the direct CML technique. Testing against a panel indicated the presence of circulating cytotoxic lymphocytes with specificity towards HLA--A2. When tested against selected HLA--D homozygous typing cells, the pattern of CML reactivity closely resembled the pattern of MLC-typing responses, i.e. typing responses were mostly restricted by the presence of HLA--A2 on the stimulator cells. This pattern was also found when time course studies of Cr--51 release were performed using experimental conditions identical to ordinary MLC typing, but involving chromium-51 labeled, irradiated homozygous typing cells as targets. These studies indicate that the presence of in vivo educated cytotoxic lymphocytes among the responder lymphocytes may in some instances mimic typing responses. Such lymphocytes are thought to lyse relevant stimulator lymphocytes prior to initiation of the proliferative response.
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PMID:False HLA--D assignments may be caused by cytotoxic responder lymphocytes. 8 Aug 33

An individual, BK, repeatedly gave typing responses against homozygous typing cells representing more than two HLA--D antigens. Family studies showed that she had inherited the HLA--Dw2 and Dw7 determinants, in agreement with results from primed lymphocyte typing. The HLA--A, B, C types of the stimulators giving rise to unexpected typing responses all involved the HLA--A1, A3 or A11 antigens. The hypothesis of this specificity in low-responsiveness was confirmed in the independent stimulator sample provided by the 7th workshop homozygous typing cell panel. The same pattern was observed when BK was tested as a responder towards related and unrelated heterozygous stimulators. Furthermore, in three-cell experiments it was found that BK cells were able to suppress the response to the Dw-identical individual, BS, towards stimulators carrying HLA--A1, A3, or A11. This effect of BK's cells appeared to be radiosensitive. We were not able to demonstrate suppressive supernatant factors in the relevant cultures, neither were we able to find circulating cytotoxic cells by the direct CML-technique, nor an accelerated cytotoxic response by the indirect CML-technique against targets carrying HLA--A1 or A3. This is the first demonstration of induction of suppressor cells in MLC by HLA--A, B, C antigens in the stimulator cells.
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PMID:Low responsiveness in MLC induced by certain HLA--A antigens on the stimulator cells. 8 Aug 34

The histocompatibility loci of the MHC can be separated into two functionally distinct types. One, loci first defined by lymphocyte reactivity in MLC, LD loci, the phenotypic expression of which leads to proliferation of allogeneic T cells, and two, serologically defined, SD loci, products of which act as targets for cytotoxic lymphocytes. Although the SD loci may be definable by both serological techniques and by lymphocyte reactions in CML, and it may well be that the LD loci products will be defined serologically, the functional difference between them is documented by the apparently converse roles in MLC and CML. The LD loci are most effective in leading to MLC stimulation and do not function as targets in CML for reasons discussed elsewhere; the SD loci function poorly it at all in stimulating proliferation in MLC but are excellent targets in CML. A cellular dichotomy may exist in reaction to these different genetic components of the MHC.
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PMID:Genetic control of major complex histocompatibility antigens. 12 15

The effect of azathioprine on in vitro baboon lymphocyte function tests was evaluated using the mitogen stimulation test, the mixed lymphocyte culture test, the migration inhibition factor test, the cell-mediated lymphocytotoxicity test and the antibody dependent cell-mediated cytotoxicity test. It was found that azathioprine inhibited phytohemagglutinin and Concanavalin A stimulation at lower concentrations than those required to inhibit pokeweed mitogen stimulation. It inhibited the MLC reaction with as little as 0.2 mug/culture in the microculture system. Azathioprine had no effect on (a) the release of migration inhibition factor, (b) the cell-mediated lymphocytotoxicity assay if presensitized cells were used, and (c) the antibody-dependent cell-mediated cytotoxicity assay. However, azathioprine inhibited CML if it was added during in vitro sensitization and induction of killer cells. These in vitro results suggest that azathioprine inhibits those reactions which require cellular division.
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PMID:The immunosuppressive mechanism of azathioprine. I. In vitro effect on lymphocyte function in the baboon. 12 57

Tolerance was induced against cytotoxic target determinants coded for by genes of the I region. Neonatal recipients were immunized with high doses of cells from an I region incompatible donor. Nonreactivity in adult life did not reflect extensive donor cell chimerism, since the great majority of cells in spleens of animals rendered tolerant were of host phenotype. Although specific nonresponsiveness in CML could be induced by these protocols, the MLC proliferative response was in most cases still present alghough very much decreased. In only a very occasional animal was complete nonreactivity in MLC seen. The nonresponse in CML was paralleled by acceptance of thyroid allografts as measured by radioactive iodine incorporation and morphological studies.
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PMID:Tolerance induction to H-2 central region target antigens: in vivo/in vitro correlations. 14 1


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