RESUMO
Target cell lysis by most murine cytotoxic T lymphocytes appears to be mediated by a complement (C9)-like protein called perforin, contained in high-density cytoplasmic granules. These granules also contain high levels of serine esterase activity, which may also play a role in cytolysis. Analysis of 17 cloned human cytotoxic T lymphocytes revealed the presence of serine esterase that is very similar to its murine counterpart in substrate and inhibitor specificities, pH optimum, and molecular mass; dot blot hybridization with synthetic oligonucleotides corresponding to the active sites of two known murine CTL esterases suggests homology to the murine enzyme HF. However, serine esterase was present at only approximately 10% of the level found in murine CTLs, and was not secreted during CTL-target cell interaction; moreover, hemolytic activity could not be detected in any of the seven cell lines tested. The results suggest that the human CTLs examined here kill their target cells by a mechanism different from that used by most cloned murine CTLs.
Assuntos
Células Clonais/enzimologia , Citotoxicidade Imunológica , Esterases/metabolismo , Hemólise , Linfócitos T Citotóxicos/enzimologia , Linhagem Celular , Centrifugação com Gradiente de Concentração , Células Clonais/imunologia , Células Clonais/metabolismo , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Esterases/antagonistas & inibidores , Esterases/genética , Humanos , Concentração de Íons de Hidrogênio , Isoflurofato/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismoRESUMO
We retrospectively analyzed the relationship between rheumatoid factor (RF) and renal disease in 102 patients with systemic lupus erythematosus (SLE). We found a significant negative association between detectable RF at any time in a patient's course and clinically significant renal diseases. Multivariate analysis indicates that RF and cryoglobulins, operating independently, have a significant and opposite association with the development of renal disease in patients with SLE. These associations appear to be unrelated to the presence or absence of anti-ds-DNA (anti-DNA). Patients with SLE who are RF negative and cryoglobulin positive are likely to develop renal disease whereas those who are RF positive and cryoglobulin negative are very unlikely to do so. The addition of RF and cryoglobulin determinations to the data base of patients with SLE appears to be clinically useful.