Anti-Idiotypic Network Induced by T Cell Vaccination Against Experimental Autoimmune Encephalomyelitis

Abstract

In a study of the mechanism of resistance to autoimmune disease induced by T cell vaccination, rats were vaccinated against experimental autoimmune encephalomyelitis (EAE) by injecting them once in the hind footpads with a subencephalitogenic dose (10(4)) of a clone of T lymphocytes specific for myelin basic protein (BP). The response to vaccination was assayed by challenging the rats with an encephalitogenic dose (3 X 10(6)) of T lymphocytes of this BP-specific clone. Five to six days after vaccination, the cells responsible for mediating resistance to adoptively transferred EAE were concentrated in the popliteal lymph nodes draining the vaccination site. Transfer of the draining lymph node cells to unvaccinated rats led to loss of resistance in the donor rats and acquisition of resistance by the recipient rats. Limiting-dilution cultures of the draining lymph node cells were established with irradiated cells of the BP-specific clone as stimulators. Two sets of T lymphocytes specifically responsive to the BP-specific T cells from the clone were isolated: CD4+CD8- helper and CD4-CD8+ suppressor cells. The helper T cells, like the BP antigen, specifically stimulated the BP-specific vaccinating clone. In contrast, the suppressor T cells specifically suppressed the response of the BP-specific vaccinating clone to its BP antigen. These results suggest that T cell vaccination induces resistance to autoimmune disease by activating an antiidiotypic network.

The effects of prophylactic cyclosporin A on experimental allergic neuritis (EAN) in the Lewis rat. Induction of relapsing EAN using low dose cyclosporin A

“…CsA is known to affect immunoregulation because under certain circumstances CsA can induce autoimmune disease (Sakaguchi and Sakaguchi, 1989) and syngeneic graft-versus-host disease (Fischer et al, 1989). There are a range of different regulatory cells including suppressor-inducer cells (Morimoto et al, 1985), contrasuppressor cells (Ptak et al, 1988), anti-idiotypic cells (Lider et al, 1988) and anti-ergotypic cells (Lohse et al, 1989) which could be affected by CsA. Different effects of low dose CsA on these cells compared to CD4 + effector cells could interfere with suppression of disease.…”

Lymphocyte vaccination protects prediabetic non-obese diabetic mice from developing diabetes mellitus

“…CD4 staining was not significantly different in the saline and NOD vaccine treated mice has been proposed that regulation of autoimmune disease is controlled by interactions between a network of suppressor and cytotoxic cells [14], and there is considerable evidence for both of these populations existing in NOD mice [15±17]. It is further suggested that raising an immune response to a vaccine composed of autoreactive T cells activates an anti-idiotypic set of regulatory lymphocytes capable of suppressing or eliminating cells infiltrating the target organ, thus allowing recovery [3,6,18]. Studies in the experimental animal model of multiple sclerosis and early clinical trials in multiple sclerosis patients have provided evidence that vaccination with attenuated autoreactive T cells does indeed stimulate such an anti-idiotypic response.…”

Remission of experimental autoimmune hepatitis is associated with antigen-specific and non-specific immunosuppression

“…Similar to our study in EAH, he found Ihis suppression lo be associated with the beginning of recovery. Study of olher animal models, in particular experimental auloimmune encephalomyelilis, have led to the identification of T cell regulatory cycles recognizing both specifically lhe responsible pathogenic T cells (anliidiotypic response) [10] and Ihc activation state of these Teells (anti-ergotypic response) [II]. In addition, antigen-specific suppressor cells have also been identified [ 12], Furthermore, lhe secretion of the immunosuppressive eylokine transforming growth factor-beta (TGF-y?)…”