Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:The genetics of cell-mediated lympholysis. 6 6

Lymphocytes sensitized against HLA-A and B region-compatible, HLA-D region-incompatible stimulators were cytotoxic for target cells having the correct HLA-D antigens. This form of cytotoxicity was inhibited by platelet-absorbed pregnancy sera containing antibodies to the HLA-DR antigens of the target cells but not by sera with antibodies against other DR antigens. This form of CML was also inhibited by unlabeled monocytes and B cells of the relevant HLA-D specificity but not by T lymphocytes from the same donors.
 ...
PMID:Specific inhibition of T-cell-mediated cytolosis by alloantiserum against HLA-D-related (DR) antigens. 8 98

It now appears unequivocal that three markers exist in a linkage group in chromosome 6 of man: HLA-A, HLA-B and PGM3 (Fig. 1.) Tentatively, two other HLA loci and one Ir gene have been mapped close to HLA-B. The probable map order is HLA-A - HLA-C - HLA-B - HLA-D - Ir. The biological functions of these loci are unknown. However, HLA-A, B and C are important in allograft rejection. Other closely linked loci (HDR, CML) appear to be important in the first events of the allograft rejection (first set) and in generation of killer cells. HLA-D might be important in cellular recognition and graft-versus-host reactions (matching at HLA-D decreases the incidence and severity of graft-versus-host disease), and the Ir genes in the defense against infections. HLA-B and HLA-D loci are important markers in studies of disease susceptibility. HLA-B locus antigens HLA-B27 and HLA-B8 are frequently associated with arthritic or autoimmune disorders. HLA-D determinants have been found in association with multiple sclerosis and C2 deficiency (HLA-DW2); juvenile diabetes and Addison's disease (HLA-DW3) and adult type of rheumatoid arthritis (HLA-DW4).
 ...
PMID:Immunogenetic aspects of allotransplantation. 13 74

The functions of the genes included in the HLA complex have been studied mainly through the allogenic response, in vitro and in vivo. The sequence of this response was established thanks to primary and secondary MLC and CML. It appears that at least two clones of T lymphocytes are involved, the first in the non-self recognition through HLA-D differences, and the second in immunization against the HLA-A and B incompatibilities. Many associations between HLA and diseases have been found. They can be classified in three categories according to their associations with HLA-B, D, or with another gene of the complex. They are true experiments of nature which will give clues to the physiological functions of the HLA complex genes.
 ...
PMID:[Physiology and pathology of the HLA complex (author's transl)]. 30 Jun 3

Investigating HLA-A, HLA-B, HLA-C, and HLA-DR antigens, MLR, CML, and PLT reactivity in two unrelated persons it was found that despite their HLA-D/DR identity cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the necessary proliferative impetus for the generation of CTL.
 ...
PMID:HLA-D/DR identity results in a positive CML reaction. 265 91

Investigating HLA-A, -B, -C, -DR and -Dw antigens and MLR, CML, and PLT reactivity in two unrelated persons, it was found that, despite their HLA-D/DR identity, cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the proliferative impetus for the generation of CTL.
 ...
PMID:HLA-DP antigens provide the proliferative impetus for the generation of cytotoxic T lymphocytes. 326 48

The specific cellular immunity of renal transplant recipients was investigated by MLR & CML. MLR has been thought to reflect the disparity of HLA-D locus between two individuals and CML to represent an in vitro model for graft rejection and graft adaptation. Anti-donor and anti-control reactivities were diminished in MLR immediately after transplantation even during acute rejection. These MLR suppression are probably due to immuno-suppressive drugs. In acute rejection episode, CML reactivity against donor was elevated and well correlated with clinical findings, but on the other hand, MLR reactivity was suppressed. This discrepancy indicates that strong MLR is not needed to induce high CML. The in vitro development of cytotoxic T cells as a result of proliferation in MLR is impaired in long term survivors and quiescent recipients after transplantation. These suppression is directed to specific donor but not to unrelated third party cells. I have demonstrated the MHC restricted CML suppressor T cell by using HLA identical monozygous twin's lymphocyte. This suppressor T cell may prove to be of value in enhancing graft acceptance and play a part of immunomodulations.
 ...
PMID:[Analysis of specific cellular immunity in renal transplant recipients by MLR & CML]. 623 57

The HLA-D/Dr region in man encodes major determinants which stimulate T lymphocytes to proliferation. The genetic organization of this region is apparently complex and is at present largely unknown. One obstacle is the scarcity and quality of available typing reagents. In an attempt to obtain high quality anti-DR sera, a series of active immunizations was performed between highly selected, healthy unrelated donors and recipients. One recipient (AR8) was immunized using cells incompatible for HLA-A2, B40 (w60), Cw3 and D/DRw6 and readily developed anti-A2 and B40 antibodies but no anti-C, CR, or other antibodies. When tested against his HLA genotypically fully identical brother using te cellular MLC, PLT, or CML techniques before immunization, results were mutually negative as expected. Following immunization, however, AR8 was able to mount MLC, PLT, and possibly CML responses against lymphocytes from the brother while the reverse combinations remained negative. When tested in the family the trait(s) thus identified seems to be maternally inherited. These results suggest the existence of minor histocompatibility determinants encoded from regions not closely linked to HLA. The brother of AR8 and the immunizing donor thus seem to share one or more determinants not possessed by AR8.
 ...
PMID:One-way positive cellular reactions between two HLA-A, B, C, D/DR genotypically identical brothers following active allogeneic immunization. 641 87

This report describes the influence of HLA-D/DR antigen disparity upon the level of cytotoxicity in allogeneic in vitro cultures. Allogeneic cultures, between unrelated HLA-D/-DR full house donors, tested in CML gave three different levels of cytotoxicity, termed weak, intermediate and strong cytotoxicity. HLA-D/-DR compatibility predicts weak cytotoxicity and two HLA-B antigen incompatibility predicts strong cytotoxicity. On the contrary, HLA-A antigens have no major influence upon the strength of cytotoxicity. Accepting that the MLC/CML reaction is an in vitro parallel to the in vivo transplantation of allogeneic tissue, the observations are in accordance with the results of HLA-D/-DR matching for graft survival in human renal transplantation.
 ...
PMID:Influence of HLA-D/DR antigen disparity in CTL generation in vitro. 660 61