Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Culture of human peripheral blood lymphocytes (PBL) in purified natural or recombinant interleukin 2 in the absence of exogenous antigen or mitogen causes the differentiation of nonlytic precursor cells into lymphokine-activated killers (LAK). A titration of purified Jurkat IL-2 (BRMP, FCRC, NIH) IL-2 showed that the relatively low concentration of 5 U/ml was optimal for LAK activation. When the responding PBL were pretreated with either mitomycin C or gamma irradiation, LAK activation did not occur, indicating that proliferation, in addition to differentiation, is required. The spectrum of target cells susceptible to LAK lysis in a 4-hr chromium-51-release assay includes fresh NK-resistant tumor cells and trinitrophenyl (TNP)-modified autologous PBL. Unmodified PBL are not lysed. Cold target inhibition studies indicated that LAK lysis of autologous TNP-PBL is totally inhibited by fresh tumors cells, and that tumor lysis is inhibited by TNP-PBL. Additionally, allogeneic tumors totally inhibit lysis of autologous tumor cells in other cold target studies. These results demonstrate that the lytic activity expressed by LAK is not HLA restricted, is not limited to tumor cells, and is "polyspecific" as indicated by the cross-reactive recognition of multiple target cell types in these cold target inhibition studies.
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PMID:The human lymphokine-activated killer cell system. V. Purified recombinant interleukin 2 activates cytotoxic lymphocytes which lyse both natural killer-resistant autologous and allogeneic tumors and trinitrophenyl-modified autologous peripheral blood lymphocytes. 392 75

A total of 78 consecutive HLA nonidentical living related donor transplant recipients with moderate to high stimulating mixed lymphocyte culture indexes underwent a deliberate donor-specific blood transfusion protocol. Of the patients 67 were first and 11 were second allograft recipients. Patients were monitored for immunological responses by cytotoxic B-cold, B-warm and T-warm antibody responses to a random panel of 30 donors, and by serial crossmatches to their donor subset B and T lymphocytes at 5C and 37C before beginning the protocol and after each donor-specific blood transfusion. Patients were followed from 3 months to 2 1/2 years, with allograft survival rates reported by the actuarial method. Survival rates of first allograft recipients were 96.0 plus or minus 2.77, 93.97 plus or minus 3.37, 93.97 plus or minus 3.37 and 90.68 plus or minus 4.50 per cent at 3 and 6 months, and 1 and 2 years, respectively. Of the patients entering the protocol for a primary transplant 20.18 per cent had persistently positive crossmatches. With increasing numbers of previous random blood transfusions a statistically significant sensitization rate was noted. Patient sensitization showed a general pattern of initial development of B-warm lymphocytotoxins resulting in positive B-warm crossmatches, which progressed to T-warm lymphocytotoxins and positive T-warm crossmatches if donor-specific blood transfusions continued. However, on development of B-warm positive crossmatches reversion to a negative crossmatch with successful transplantation was possible upon cessation of transfusions. No patient in the study was rendered nontransplantable due to donor-specific blood transfusions. All 5 patients who were completely disparate suffered amnestic type rejection episodes but following control of the rejection the course mimicked that of mixed lymphocyte culture identical living related donor transplants. Donor-specific blood transfusion is highly successful among first allograft recipients and success in extending the procedure to more disparate relatives is noted.
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PMID:Improved allograft survival in nonidentical living related donor transplants using donor-specific blood transfusions. 397 87

Sixteen (24%) of 68 patients with aplastic anemia had antibodies cytotoxic to their own lymphocytes before specific disease treatment. These antibodies displayed the characteristics of cold reactive lymphocytotoxins (LTs). No correlation existed between the detection of auto-LTs and a viral or toxic cause of the disease or the patients' HLA genotype. A lower frequency of anti-HLA antibodies was recorded in the pretreatment sera of patients with auto-LTs. However, the response rate to antilymphocyte serum treatment and the outcome of the bone marrow grafts were comparable among the patient's groups with or without pretreatment auto-LTs.
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PMID:[Incidence, characteristics and clinical importance of autolymphocytotoxins in aplastic anemias]. 408 81

Cytotoxic T lymphocytes (CTL) against autologous EBV-transformed B lymphoblastoid cell line (LCL) were induced in vitro by culturing peripheral blood lymphocytes (PBL) of healthy donors together with mitomycin C-treated autologous LCL for 6 days. The cytotoxic cells developed only from the E-rosette-positive fraction but not from the negative fraction of PBL. These CTL killed autologous LCL but not PWM-stimulated autologous PBL. In addition, the CTL killed allogeneic LCL when at least 1 of the HLA-A antigens was identical with that of the LCL of CTL donor. However, identity of HLA-B and HLA-C antigens was not enough for a significant killing of allogeneic LCL. The specificity of the CTL was also confirmed by a cold target inhibition test. These results indicated that the CTL induced specifically recognized EBV-transformed cells with HLA restriction.
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PMID:In vitro induction of HLA-restricted cytotoxic T lymphocytes against autologous Epstein-Barr Virus transformed B lymphoblastoid cell line. 616 15

A case of a 35-year-old female with multiple sclerosis is reported who developed without apparent prior sensitization a lymphocytotoxic antibody with anti-HLA-B8 specificity. The antibody persisted for several years with the same titer. The cytotoxic activity of the patient's serum was contained within the IgM fraction. The antibody reacted optimally at low temperature, exclusively against lymphocytes homozygous for HLA-B8. In B8-heterozygous cells, cytotoxic reactions were obtained only following enzymatic pretreatment. The antibody's binding avidity was weak; for its complete absorption, many times more B8-positive lymphocytes or platelets were needed than for a "normal" anti-B8 antibody of the same titer. In HLA redistribution and blocking experiments, it was demonstrated that the antigenic determinant recognized by this antibody is carried by the B8 molecule. It is unclear whether "spontaneously" occurring cold-reactive IgM antibodies with HLA specificity are induced by viral agents or whether they reflect "spontaneous" clonal lymphocyte proliferation.
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PMID:A "spontaneous" cold-reactive IgM antibody with anti HLA-B8 specificity in a patient with multiple sclerosis. 617 60

Three patients from two families with complete hereditary deficiency of the fourth component of complement (C4) and systemic lupus erythematosus are described. The syndrome presented by these patients is characterized by early onset in life; exquisite sensitivity to sunlight and to cold exposure, the latter resulting Raynaud's phenomenon; and skin lesions involving not only exposed areas of the body but also palms and soles and presenting as butterfly rashes, maculopapular eruptions, and lesions similar to those of chronic discoid lupus erythematosus, with marked scaling, atrophy, and scarring. Lupus erythematosus (LE) cell tests were negative and antinuclear antibody (ANA) titers low or negative. The male patient of our series died at the age of 31/2 years from septicemia, whereas the two girls, aged 18 and 11 years, respectively, were alive at the time of writing. The C4-deficient gene is associated with HLA-Aw32, Bw38, and Bf S in one family and with HLA-A30, B18, DR7, and Bf S1 in the other family; the latter is the second family in which this HLA haplotype has been found to be associated with hereditary C4 deficiency.
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PMID:Systemic lupus erythematosus in hereditary deficiency of the fourth component of complement. 617 71

Possible immunogenic heterogeneity of the HLA-Bw44 antigen was investigated using cytotoxic T lymphocytes (CTL) generated between donors identical for HLA-A2,3,-B7,w44. Highly discriminatory CTL combinations were identified that defined two subgroups of Bw44, designated 44.1 and 44.2. Out of 47 Bw44-positive donors tested in a population study, 30 were lysed by the CTL defining 44.1, and 19 were lysed by the CTL defining 44.2. All Bw44 cells could be typed as either 44.1 or 44.2, except two Bw44-positive cells that were phenotypically homozygous for the serologically defined Bw44 antigen and were lysed by both CTL. No Bw44-negative donors (zero out of 37) expressed either 44.1 or 44.2, although cold target blocking was required to eliminate a contaminating reactivity of one CTL population on Bw35 and some Bw45 cells. CTL were also raised between responder/stimulator combinations mismatched for Bw44. These CTL lysed all Bw44-positive target cells, indicating a CML antigen shared by all Bw44 cells. But clear discrimination of the 44.1 and 44.2 subgroups was obtained when appropriate cold target blocking cells were added. All donors with 44.2 expressed high levels of serologically detectable Bw44 on their platelets, and all with 44.1 expressed low levels (p less than 0.005). Furthermore, population studies indicate that 44.1 is in positive linkage disequilibrium with HLA-A2 and possibly DR4, whereas 44.2 is in positive linkage disequilibrium with HLA-DR7 and possibly HLA-A23, -A26, and -A29. These data suggest the existence of two genetically and functionally different subgroups of Bw44 antigens.
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PMID:Two subgroups of HLA Bw44 defined by cell-mediated lympholysis that differ in Bw44 expression on platelets and in patterns of genetic linkage disequilibrium. 618 11

Fetal calf serum (FCS) generated at least two distinct populations of human cytotoxic cells in vitro. One population expressed natural killer (NK) cell-like activity and lysed K562 and HSB-2 targets more effectively than autologous or allogeneic lymphoblastoid cell lines (LCLs). The other population contained FCS-specific cytotoxic T cells which preferentially lysed the autologous LCLs and showed minimal lysis of K562. E-rosette separation and cold target competition experiments clearly established that NK cells were not involved in the self-reactive lysis. Moreover, the lytic activity of the E-rosetted T cells was reduced by up to 95% when autologous target cells were grown in human AB serum rather than FCS, showing that FCS-associated determinants on targets were essential in the cytolytic phase. Autologous LCLs grown in FCS were also considerably stronger competitors than human serum-grown LCLs. The consistent self-preferred lysis suggested that HLA antigen-related restriction was involved, but the patterns of lysis did not implicate HLA-A or B antigens, and monoclonal antibody (W6/32) to an A, B, and C monomorphic determinant failed to block FCS-specific lysis. In contrast, monoclonal antibody (DA.2) to a monomorphic determinant of DR effectively blocked FCS-specific lysis. Cytotoxicity tests with a small panel of DR-typed donors indicated that strong cross-reactions were invariably associated with sharing of DR antigens, particularly DR2, and to a lesser but significant extent DR7. Although DR antigen sharing did not always result in lysis of allogeneic targets, the overall evidence strongly suggests that FCS-specific T-cell cytotoxicity in humans is restricted by products encoded by or associated with the DR genes.
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PMID:Evidence for the involvement of HLA-DR antigens in restricted cytotoxicity by fetal calf serum-specific human T cells. 618 49

Eight cloned T cell lines specific for Epstein Barr virus-transformed B lymphocytes were derived. In the presence of the autologous virus-infected B cells, the T cell lines show HLA-restricted cytotoxic activity and also secrete alpha-interferon in sufficient amounts to inhibit infection and transformation. Four of these clones showed restriction to a single HLA locus (two for A3, and two for B7) and three showed exquisite self-restriction lysing only autologous targets. These seven clones expressed the classical cell surface phenotype of cytotoxic T cells being T3, 8, 11, and la-positive and T4-negative. An eighth clone that lacked the T8 surface marker appeared to recognize both B7 and BW51. HLA restriction was confirmed: 1) by the ability of a monoclonal antibody against an HLA-A,B,C framework antigen (W6-32) to block the cytotoxicity; 2) the failure of the clones to lyse Daudi, an EBV-positive, HLA-A,B, C-negative cell line; and 3) successful competition of the cytotoxicity by autologous but not allogeneic cold targets. The cloned T cells do not kill EBV-negative targets such as autologous pokeweed mitogen blasts and cell lines including CEM and the natural killer cell target K562. The results suggest T cell clones may be generated against an EBV-associated membrane antigen on transformed B cells, perhaps equivalent to the lymphocyte-determined membrane antigen, and that the recognition is restricted by a single HLA determinant. We propose that single T cells can play multiple roles in controlling EBV infection in vitro and in vivo including the elimination of transformed cells by cytotoxicity and the prevention by secreted interferon of further re-infection and transformation.
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PMID:Analysis of cellular immune response to EBV by using cloned T cell lines. 618 40

Human cytotoxic T cells (Tc) specific for autologous adult T cell leukemia virus- (ATLV) bearing cells were induced in vitro. Peripheral blood leukocytes (PBL) from healthy donors were stimulated repeatedly with autologous ATLV-bearing T cells. In two out of four seropositive donors and one out of two seronegative donors, the responder cells showed cytotoxicity for autologous ATLV-bearing cells, but not for autologous PBL, autologous cloned T cell lines, Epstein Barr virus-transformed autologous lymphoblastoid B cell line (LCL) cells, or various ATLV-negative cell line cells. The effector cells induced were cytotoxic T cells possessing Leu-1 and Leu-2a antigens that were able to proliferate continuously in vitro with periodic restimulation by appropriate cells and supplementation with partially purified T cell growth factor (TCGF). Of three Tc lines tested, one exhibited significant cytotoxicity against allogeneic ATLV-bearing cells that shared HLA-A2 antigen with the effector cells, possibly indicating HLA-restriction of ATLV-specific Tc. HLA-restriction was also suggested by cold target inhibition of cytotoxicity. Interestingly, Tc from this individual could also kill fresh adult T cell leukemia cells that were not expressing the ATLV surface antigens. These results, together with the target specificities of other Tc lines, suggest the possibility of at least two distinct target antigens recognized by ATLV-specific Tc, with one of these antigens differing from the ones detected by serologic methods.
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PMID:Establishment of human cytotoxic T cell lines specific for human adult T cell leukemia virus-bearing cells. 618 6


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