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)

We have investigated HLA-DR beta 3-associated functional polymorphism using selected Epstein-Barr virus (EBV) specific human T cell clones and EBV-transformed B cell (EBV-B) lines. To study the relationship between T cell recognition and the gene products of the three alleles of the DR beta 3 locus, Dw24, 25 and 26 (these were previously called DRw52a, b and c, respectively), CD4+ cytolytic T cell clones (CD4+ CTL) were isolated by repeated stimulation of peripheral blood mononuclear cells (HLA A2 A24; B8 B27; DRw17, Dw24, DRw2) with autologous EBV-B. Clone no. 32 proliferated strongly in response to HLA-Dw24 EBV-B, but not to Dw25 or Dw26 EBV-B. Furthermore, clones no. 32 and no. 45 both lysed HLA-Dw24 EBV-B but not Dw25 or Dw26 EBV-B. In addition, cold target inhibition studies showed that the cytolytic activity of both clones was blocked by unlabelled HLA-Dw24 EBV-B, but not by Dw25 or Dw26 EBV-B. Clones no. 32 and no. 45, therefore, could distinguish between the three allelic products of DR beta 3 haplotypes.
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PMID:CD4+ cytolytic T cell clones that recognize polymorphism of HLA-DR beta 3 chains. 216 3

Among 331 recipients of cadaveric renal allografts, transplanted from 1976 to 1986 at the Rostock Transplant Center the graft survival rates have been analyzed. All patients have been treated by conventional immunosuppressive therapy using azathioprine and prednisolone. A relation between graft survival and immunological factors was found: the better the HLA match, the better the transplant results. The necessity of a restrictive transfusion regime was stressed. The higher the number of pretransplant transfusions, the higher is the panel reactivity with following lower graft survival. Cold ischemic time was without influence on graft survival. The introduction of cyclosporin may improve the graft survival rate as known of 10-20%.
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PMID:[Factors influencing the result of kidney transplantation with special reference to the HLA system in conventional immunosuppression]. 223 84

To assess the impact of cadaver donor age on posttransplant renal function and graft survival, we analyzed our clinical results in 17 recipients of younger donor kidneys (less than 10 years) and 48 recipients of older donor kidneys (greater than 50 years) and compared them with a control group of 598 patients who received kidneys from donors between 11 and 50 years of age. The 3 groups were comparable with respect to recipient age, duration of dialysis, prior transfusions, previous transplants, cold ischemia time, HLA AB mismatches, cytotoxic antibody profile, posttransplant ATN, and prophylactic ALG treatment. The cumulative patient survival at 1, 2, and 3 years was not significantly different among the 3 groups, but the graft survival in recipients of older donor kidneys was significantly lower than the control (71% vs. 62% at 2 years, P = .09 and 66% vs. 55% at 3 years, P = .0003. The short-term renal function assessed at 1 month posttransplant was significantly lower in the older donor group compared with the control (creatinine clearance 45 mL/min vs. 59 mL/min, P = .0003). Likewise, the long-term renal function assessed at the last follow-up was also lower in the older donor group than the control (creatinine clearance 40 mL/min vs. 49 mL/min, P = .07). There were no significant differences in graft survival or short- or long-term renal function between the younger donor group and the control group. These observations suggest that transplantation of a kidney from an older cadaver donor is associated with an inferior posttransplant outcome. The practical decision whether or not to use an older donor kidney should be individualized taking this as well as other factors into account.
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PMID:Influence of cadaver donor age on posttransplant renal function and graft outcome. 230 Oct 36

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.
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PMID:The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era. 230 66

We compare the results in recipients of cadaveric renal allografts immunosuppressed with cyclosporine and prednisone to those who received immunosuppression with cyclosporine, azathioprine and prednisone. The 2 groups were compared relative to HLA-ABDR matching, plasma reactive antibodies, cold ischemia time, diabetes as a cause of renal failure and recipient age greater than 50 years. The incidences of clinical allograft rejection and grafts lost to rejection were not significantly different in these 2 groups evaluated at 1 year. In the 2-drug immunosuppressed group the actual 3, 6 and 12-month graft function was 87, 86 and 85%, respectively, compared to 79, 78 and 74%, respectively, in the 3-drug immunosuppressed group. A difference in graft survival was due to graft loss secondary to vascular thrombosis and patient death, and not to immunological events. No advantage was demonstrated for the use of 3-drug immunosuppression for kidney allografts over a 2-drug protocol of cyclosporine and prednisone.
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PMID:Comparison of 2-drug and 3-drug immunosuppression for cadaveric renal transplantation. 232 2

Autologous tumor-specific cytotoxic T-lymphocytes (CTLs), generated by repeated stimulation with autologous melanoma and expanded in interleukin 2, are major histocompatibility complex restricted. These CTLs recognize a common tumor-associated antigen in the presence of HLA class I determinants, suggesting that allogeneic melanomas which express the restricting HLA-A region antigen could substitute for the autologous tumor in the generation of CTLs. This was investigated in the HLA-A2 system. Four T-cell lines were established by stimulation of lymphocytes with either autologous tumor or an HLA-A2-matched allogeneic melanoma. Allogeneic stimulated CTLs specifically lysed the autologous tumor and demonstrated an identical pattern of HLA-A2 restriction, when compared to the autologous stimulated CTLs. Lysis by the allogeneic stimulated CTLs was blocked by a monoclonal antibody to HLA class I antigens; lysis was also inhibited by both autologous tumor or HLA-A2 allogeneic melanomas when evaluated in cold target competition studies. The allogeneic stimulated CTLs proliferated in response to both autologous tumor and HLA-A2 melanomas, but not in response to HLA-A2 nonmelanomas. By phenotypic analysis these CTLs were CD3+ and predominantly CD8+ cells. We conclude that autologous tumor-specific CTLs can be generated using HLA-A region-matched allogeneic melanomas for stimulation. Since established, HLA-typed melanoma tumor lines can be used in the absence of autologous tumor; this procedure can be applied clinically to a broad patient population and may prove useful in the adoptive immunotherapy of melanoma.
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PMID:Generation of human autologous melanoma-specific cytotoxic T-cells using HLA-A2-matched allogeneic melanomas. 240 72

The HLA-B27 antigen may be divided into at least three subgroups, designated HLA-B27.1, -B27.2, and -B27.3, by specific cytolytic T lymphocytes. In an attempt to explore the functional relevance of HLA polymorphism, an alloimmune cytolytic T cell clone T3+, T8+, T4- has been characterized, which displays a distinct reactivity pattern with each one of the three HLA-B27 subtypes. This cell kills both B27.1- and B27.2- but not B27.3-positive targets. Its lytic efficiency is greater with B27.1 than with B27.2 cells. The clone does not recognize either B7-positive targets or most B27-negative cells. But HLA-B40-bearing cells are lysed, albeit with significantly less efficiency than any B27-positive targets. The differences in killing ability for B27.1, B27.2, and B40 are also evident in cold-target inhibition studies, indicating that a) B27.1 cells can efficiently inhibit lysis of B27.2 and B40 targets, b) B27.2 cells inhibit the lysis of B40 but not of B27.1 targets, and c) B40 cells do not inhibit B27.1 or B27.2 target lysis. In addition, anti-T3 and anti-T8 antibodies are much more effective in inhibiting the lysis of B27.2 targets than that of B27.1-positive cells, suggesting that the observed differences in killing efficiency of the various targets are due to the fact that the tightness of the effector-target interaction is affected by the structural changes between the different HLA antigens. A correlation of the reactivity pattern of this T cell clone with the known amino acid sequences of the HLA-B27, HLA-B40, and HLA-B7 antigens suggests that the clone recognizes a conformational determinant contributed to by residues within the segments 149-156 and 67-83. Those in the former segment appear to be an essential portion of this determinant, whereas polymorphism in the region 67-83 has a modulating effect on the reactivity of the effector but does not abrogate recognition.
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PMID:One allogeneic cytolytic T lymphocyte clone distinguishes three different HLA-B27 subtypes: identification of amino acid residues influencing the specificity and avidity of recognition. 241 11

The functional role of the T8 antigen of human T cells was studied by inhibition with anti-T8 monoclonal antibodies (mAb) of the cytotoxic action of T8+ cytotoxic T lymphocyte clones (CTL). All clones were allospecific and directed against HLA-B7. The ability of seven different anti-T8 mAb to inhibit the cytotoxicity of these alloreactive CTL clones corresponded with their avidity for a particular target cell. The lysis of cross-reactive antigen-bearing target cells was more readily blocked by anti-T8 mAb than lysis of the specific B7 target cell against which a clone was raised. The seven anti-T8 mAb showed a spectrum of CTL blocking ability ranging from strong blocking with all five CTL clones tested to weak inhibition of only two out of five clones. mAb inhibition of CTL reactivity and cold target inhibition studies with one of the five CTL clones indicate a post-binding role of the T8 molecule. Functional epitope mapping based on CTL blocking with the anti-T8 mAb resulted in the definition of one nonfunctional epitope on the T8 molecule which is only expressed on mature T lymphocytes and a cluster of closely related functional epitopes expressed on both thymocytes and mature T lymphocytes. Not only allospecific cytotoxicity, but also nonspecific cytotoxicity induced anti-T3 mAb in these allospecific clones was inhibited by anti-T8 mAb in the absence of HLA class I expression on the target cell (Daudi cell line). The hierarchy of blocking with anti-T8 mAb and the classification of functional epitopes on T8 in anti-T3-induced nonspecific cytotoxicity were similar to those obtained in blocking of allospecific reactivity of the CTL clones. This analogy points to an identical function of the T8 antigen in both allospecific and anti-T3-induced nonspecific cytotoxicity. If HLA class I molecules are the counter structures of the T8 antigen, then these results argue against an adhesion-like function of the T8 structure. The combined results show that the T8 molecule has a regulatory role in CTL activation. It is postulated that the T8 antigen might serve as a receptor that transduces a negative feedback signal for T cell activation which prevents T cell triggering by nonspecific interaction.
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PMID:Evidence for a regulatory role of the T8 (CD8) antigen in antigen-specific and anti-T3-(CD3)-induced lytic activity of allospecific cytotoxic T lymphocyte clones. 243 Aug 10

The fine specificity of nine cytolytic T lymphocyte (CTL) clones obtained after stimulation of HLA-B27- responder lymphocytes with B27.1+ lymphoblastoid cell lines has been analyzed. These clones defined three different reaction patterns when tested against a panel of target cells including those expressing all known HLA-B27 subtypes: (a) specific recognition of HLA-B27.1, B27.2 and B27d, (b) selective reactivity with B27.1, B27d and HLA-B40 and (c) selective recognition of B27.1, B27.2, B27d, B27f and B40. Representative clones within each group were analyzed in detail. Differences in lytic ability of the various susceptible targets within each group were established by cold target inhibition analyses and by blocking experiments with anti-CD3 and anti-CD8 monoclonal antibodies. When correlated with the known structure of the HLA-B27 subtypes, these results demonstrate the critical relevance of amino acid changes within residues 77-81 and at position 152 in modulating allospecific CTL recognition of HLA-B27.1 and suggest that these residues could be involved in the structure of immunodominant regions of this antigen. The observed cross-reactions with HLA-B40, differing from B27.1 in 16 amino acid residues, suggest that the simultaneous occurrence of multiple amino acid changes could have mutually compensatory effects, so that a cross-reactive epitope might result from various combinations of polymorphic residues.
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PMID:Clonal heterogeneity of HLA-B27 cellular allorecognition. Delineation of immunodominant sites. 245 Jul 55

CTL clones isolated from PBL or from tumor-infiltrating lymphocytes (TIL) of a melanoma patient (pt665) were screened for specificity on a panel including autologous tumor cells from two distinct metastases (Me665/1, Me665/2), autologous EBV-transformed B cells and 15 allogeneic cell lines of different histology. Each clone displayed a peculiar cytolytic activity ranging from lysis of most targets (PBL clone 4C4) to preferential reactivity on the two autologous metastases (TIL clone 8B3). Blocking and modulation experiments, revealed that the lysis of autologous-Tu cells by TIL clone 8B3, but not by PBL clone 4C4, could be inhibited by mAb to HLA-class I and to CD3 Ag or by CD3 complex modulation. Clone 8B3 was tested also on a panel of 25 tumor clones from Me665/2, revealing that only 4 neoplastic clones were lysed (2/4, 2/14, 2/17, and 2/51). Cold target competition experiments indicated that the uncloned autologous melanomas and one tumor clone (2/17), but no two other tumor clones (2/10, 2/15), could compete with one another for lysis by 8B3. Determination of melanin content of tumor clones from Me665/2 revealed that the four neoplastic clones recognized by 8B3 possessed much lower melanin levels than all the other 20 clones not lysed by this effector.
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PMID:Cytotoxic T lymphocyte clones from peripheral blood and from tumor site detect intratumor heterogeneity of melanoma cells. Analysis of specificity and mechanisms of interaction. 246 23


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