Novel packages of viral and self-antigens are generated during apoptosis.

Rosen, Antony; Casciola‐Rosen, Livia; Ahearn, Joseph M.

doi:10.1084/jem.181.4.1557

Cited by 241 publications

(158 citation statements)

References 17 publications

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“…This generated high concentrations of known autoantigens within discrete subcellular packages. In another study, the same group found that after induction of apoptosis by Sindbis virus infection in HeLa cells, viral antigens and autoantigens cocluster exclusively in small surface blebs of apoptotic cells (42). These blebs form antigenic structures of mixed viral and self origin and could define a novel immune context.…”

mentioning

confidence: 96%

In vitro apoptosis and expression of apoptosis‐related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases

Lorenz

Grünke

Hieronymus

et al. 1997

Arthritis & Rheumatism

170

132

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Objective. To analyze factors related to apoptosis in systemic lupus erythematosus (SLE) peripheral blood mononuclear cells (PBMC) and to compare the findings in SLE PBMC with those in normal donor PBMC or PBMC from patients with other autoimmune diseases. Methods. PBMC from normal healthy donors or patients with SLE, mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), or various vasculitides were isolated. The percentage of apoptosis after activation through different signaling pathways was quantified using propidium iodide staining. Protein expression of Fas/APO‐1 or bcl‐2, and messenger RNA (mRNA) expression of bcl‐2, bcl‐xL, bax, bak, Fas/APO‐1, Fas ligand (Fas‐L), c‐myc, mad, or max were determined. Results. We confirmed previous findings of increased numbers of apoptotic cells in SLE PBMC compared with normal donor cells after in vitro incubation. After activation of PBMC with CD28 monoclonal antibody plus phorbol myristate acetate (CD28 MAb/PMA), staphylococcal enterotoxin B (SEB), or phytohemagglutinin (PHA), the percentage of apoptotic cells was unchanged (SEB) or diminished (CD28 MAb/PMA, PHA) in SLE cells, and the difference between normal donor and SLE cells was less pronounced. On the mRNA level, expression of apoptosis‐related gene products did not differ between SLE cells and normal donor cells. Expression of Fas/APO‐1 protein was increased in freshly isolated SLE T lymphocytes compared with normal donor T lymphocytes, whereas bcl‐2 protein was up‐regulated after a 3‐day culture period. Cellular activation further increased bcl‐2 protein levels, eliminating differences between normal donors and SLE patients. In RA cells, the percentage of apoptosis was similar to that in normal donor PBMC, whereas results using cells from patients with other autoimmune diseases (MCTD, Wegener's granulomatosis, Takayasu arteritis, polyarteritis nodosa) were comparable with those found using SLE PBMC. Addition of growth factors such as interleukin‐2 (IL‐2), IL‐4, or IL‐15 to culture medium decreased the percentage of in vitro apoptosis in both normal donor and SLE cells. Conclusion. Based on these data, we conclude that accelerated in vitro apoptosis and increased Fas/APO‐1 and bcl‐2 protein expression in SLE are nonspecific for the disease, and might be explained at least in part by the increased in vivo activation levels of PBMC from patients with SLE, MCTD, or autoimmune vasculitides combined with in vitro incubation under “noninflammatory” conditions and growth factor withdrawal.

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mentioning

confidence: 96%

In vitro apoptosis and expression of apoptosis‐related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases

Lorenz

Grünke

Hieronymus

et al. 1997

Arthritis & Rheumatism

170

132

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“…Autoantigens in general have been found to have peculiarities of charge or of secondary structure [16]; or genetic polymorphisms, as in the paper by Stadler et al [5]. Particular autoantigens may have particular features: they may be mimicked by prokaryotic sequences [17]; they may have biological activities such as chemoattraction [18]; they may bind secondary receptors such as TLR9 [19]; they may traffic to apoptotic blebs [20]; they may be cleaved by apoptosis enzymes [21]; or they may undergo posttranslational modifications [22].…”

Section: Autoantigen Selectionmentioning

confidence: 99%

Do autoantigens define autoimmunity or vice versa?

Eisenberg

2005

Eur J Immunol

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The basic function of the adaptive immune system is to distinguish self from foreign. The failure of self tolerance can result in autoimmunity, which comes in many forms but still targets a limited selection of the total available autologous determinants. This selectivity must reflect the underlying mechanisms of the autoimmune reaction, as well as the particular features of the autoantigens that are targeted. Here I discuss the overall paradigm of autoimmunity, and what kinds of mechanisms might play a role. It is likely that multiple different pathways are critical in various diseases, and even in a single condition.

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“…Nearly all protein autoantigens recognized by sera of SLE patients contain cleavage sites for caspases or granzyme B. These autoantigens are specifically cleaved during apoptotic or necrotic cell death (40)(41)(42). Therefore, it can be speculated that cryptic epitopes from modified autoantigens (often referred to as altered "self") from apoptotic cells can become dominant, if the epitope hierarchy changes due to proteolysis (43).…”

Section: Apoptosis and Autoimmunitymentioning

confidence: 99%