Posttransplant obesity and hyperlipidemia: major predictors of severity of coronary arteriopathy in failed human heart allografts.

The contribution of specific risk factors to the development of coronary arteriopathy in human heart allografts remains unclear. Allografts from 15 patients, 11 males and 4 females, aged 15 to 58 years (mean, 40 years), with patient survival from 0.5 to 24 months (mean, 8.6 months) with "triple drug therapy," had the entire coronary artery trees removed, with 184 4-mm arterial segments studied. Luminal narrowing was measured by means of digitization on a video image analysis system, and extent of luminal narrowing (cross-sectional area reduction: [Intimal area/Intimal area + Luminal area] X 100 = %) was related to 40 individual risk factors, including demographic, hemodynamic, immune, environmental, and therapeutic factors. Mean luminal narrowing, considering all coronary segments, was significantly greater in patients with higher versus lower mean cholesterol levels (246 vs 163 mg/dl), triglyceride levels (328 vs 145 mg/dl), and body mass indices (31 vs 22 kg/m2) at 62% versus 38%, 59% versus 42% and 61% versus 44% luminal narrowing, respectively. Considering all coronary segments from all heart allografts, mean luminal narrowing steadily progressed with duration of implant, reaching greater than 60% within 6 months. Mean luminal narrowing was identical in proximal and distal halves of coronary trees at 51% and 50%, respectively. Rejection episodes, considering all degrees of rejection, were strongly related to percent luminal narrowing (p = 0.01). Multivariate analysis indicated the single most predictive risk factor to be posttransplant body mass index (r = 0.77; p = 0.0009).(ABSTRACT TRUNCATED AT 250 WORDS)

Reactive T cells in the immune repertoire: self-restricted and allo-restricted helper T-cell clones to Epstein-Barr virus.

Helper T-cell clones were generated by stimulation with autologous or allogeneic lymphoblastoid B cells (B-LCL) transformed by the Epstein-Barr virus (EBV). Some of these T-cell clones were allo-reactive and others were specific to EBV-transformed B-LCL. Helper T-cell clones specific to EBV-transformed B-LCL were restricted either by class-I or by class-II HLA molecules of self. T-cell clones restricted by class-I HLA molecules were stained by OKT3 and OKT8 monoclonal antibodies (MAbs), whereas class-II-restricted clones stained with OKT3 and OKT4. Not all helper T-cell clones specific to EBV-transformed B-LCL were restricted to self: one clone restricted by allo-HLA antigen was established. This finding suggests that in humans, as in mice, some T cells in the T-cell repertoire can be allo-restricted. This allo restriction may represent cross-reactivity of T cells, whereby "self + X" equals "allo + Y." Activation of these cross-reacting T cells restricted by allogeneic HLA molecules during infectious mononucleosis will give a T-cell response which may appear unrestricted by self HLA molecules. This mechanism helps to explain, at least in part, the HLA unrestricted cytotoxicity to B-LCL observed in infectious mononucleosis.