RESUMEN
We have investigated lymphocyte subpopulations and blood mononuclear cell (MNC) adhesion to activated endothelial monolayers in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy (HAM), in HTLV-I asymptomatic carriers (carriers), and in seronegative controls. HAM patients and carriers had higher levels of CD4(+)CD29(+) "memory cells" than controls (P < 0.05). The percentage of CD3(+)CD27(-) "primed T cell" was elevated in patients with HAM (P < 0.05), but not in carriers. HAM patients had higher levels of CD8(+)CD57(+) "cytotoxic cells" (P < 0.05) than controls and carriers. The percentages of CD4(+) cells coexpressing activation markers HLA-DR and CD25, and of CD8(+) cells expressing HLA-DR, were significantly higher in HAM patients and carriers than in controls. Functional experiments indicated that MNC from HAM patients adhered more to activated endothelial monolayers than MNC from carriers or controls. Blocking studies demonstrated that the adhesion molecules VLA-4 and ICAM-1 and also L-selectin all contributed to increased binding. Analysis of expression of molecules involved in adhesion indicated that in HAM patients, L-selectin (CD62L) expression on CD4(+) and CD8(+) subsets was lower than in controls. Interestingly, HAM patients had a lower percentage of CD4(+) subsets expressing L-selectin than carriers (P < 0.05). In contrast, the percentage of CD4(+) and CD8(+) cells expressing VLA-4 (CD49d) was found to be higher in both HAM patients and carriers compared with controls. After 2 days in culture without mitogen, the percentage of T cells expressing ICAM-1 (CD54) increased in culture in carriers and more profoundly in HAM, but not in controls (P < 0. 05). After culture, T cells expressing the early activation antigen CD69 were also increased in HAM and carriers (P < 0.05) but not in controls. Interestingly, the levels of CD8(+) cells coexpressing activation antigen HLA-DR and CD38 were higher in HAM patients compared with both carriers and controls (P < 0.05) after culture. These findings are consistent with the observations that HTLV-I produces chronic lymphocyte activation with increased adhesion. This may be sufficient to initiate events leading to central nervous system inflammation and ultimately to HAM.
Asunto(s)
Endotelio Vascular/inmunología , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/inmunología , Paraparesia Espástica Tropical/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Bloqueadores/farmacología , Adhesión Celular/inmunología , Moléculas de Adhesión Celular/inmunología , Línea Celular , Sistema Libre de Células/inmunología , Medios de Cultivo Condicionados/farmacología , Endotelio Vascular/citología , Células Precursoras Eritroides/efectos de los fármacos , Células Precursoras Eritroides/metabolismo , Femenino , Humanos , Interferón gamma/farmacología , Leucocitos Mononucleares/química , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Coloración y Etiquetado , Subgrupos de Linfocitos T/química , Subgrupos de Linfocitos T/inmunologíaRESUMEN
We investigated the adhesion of blood mononuclear cells (MNC) isolated from patients with HTLV-1-associated myelopathy (HAM/TSP). MNC from HAM/TSP patients were significantly more adherent to activated endothelial monolayers than MNC from non-HAM/TSP (controls and HTLV-1 carriers) subjects. Blocking studies demonstrated that the adhesion molecules VLA-4 (CD49d), ICAM-1 (CD54), and L-selectin (CD62L) all contributed to increased binding. However, anti-ICAM-1 antibody was the most efficient in inhibiting binding HAM/TSP patients MNC to activated endothelial cells. Expression on MNC of molecules involved in adhesion was also studied by flow cytometry in HAM/TSP patients, HTLV-1 carriers, and healthy control subjects after two days culture without any mitogen. In HAM/TSP patients, L-selectin expression on CD4+ and CD8+ subsets was lower than in controls; interestingly, HAM/TSP patients had lower percentage of CD4+ subset expressing L-selectin than HTLV-1 carriers. The percentage of CD4+ and CD8+ cells expressing VLA-4 was found to be similar to controls in both HAM/TSP patients and HTLV-1 carriers. Following two days in culture without mitogen, the percentage of T cells expressing ICAM-1 increased in HAM/TSP and carriers, but not in controls. This study provides information regarding trans-endothelial migration of MNC across the blood brain barrier in HAM/TSP and suggests ICAM-1 and its counterpart molecule LAF-1 are involved in massive infiltration of lymphocytes observed in the spinal cord.
Asunto(s)
Molécula 1 de Adhesión Intercelular/metabolismo , Paraparesia Espástica Tropical/metabolismo , Linfocitos T/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Endotelio/citología , Femenino , Humanos , Selectina L/metabolismo , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/genética , Paraparesia Espástica Tropical/inmunología , Linfocitos T/inmunologíaRESUMEN
Using an ELISA assay and inhibition of antibody mediated cytotoxicity we found that there was a higher level of anti-antiself activity in B6 anti-BALB/c alloimmune mice than in BALB/c anti-B6 mice. In contrast, when an inhibition of cellular cytotoxicity assay was used to assay for the activity, similar levels of anti-antiself antibodies were seen in B6 anti-BALB/c and BALB/c anti-B6 sera. Anti-antiself antibodies in alloimmune sera are not absorbed by the cellular immunogen as readily as are anti-foreign antibodies. These results are interpreted in terms of anti-antiself antibodies being directed mainly against T cell receptors specific for self. Anti-antiself antibodies are found also in old B6 mice, that are also known to make autoantibodies.