Evidence for suppressor cells in Lewis rats' experimental allergic encephalomyelitis

Adda, D.‐H.; Béraud, Evelyne; Depieds, R

doi:10.1002/eji.1830070908

Cited by 75 publications

(28 citation statements)

References 33 publications

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“…Similar mechanisms could explain our observations in EAE where n-6 PUFA-rich seed oils are protective and n-3 PUFA-rich fish oils increase severity and delay recovery (Harbige, 1993(Harbige, , 1998Harbige et al 1995Harbige et al , 2000. Natural recovery in EAE is mediated by expansion of suppressor lymphoid cells (Adda et al 1977), some of which have been characterised as TGFβ-producing CD4 + T cells by Karpus & Swanborg (1991). The protective effect of borage oil in EAE is linked to increased TGFβ transcription and production by T-cells and/or monocytes and/or PGE 2 -producing monocytes (Harbige et al 2000).…”

Section: Metabolism and Immunobiology Of Polyunsaturated Fatty Acidssupporting

confidence: 73%

Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses

Harbige

Fisher

2001

Proc. Nutr. Soc.

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Immunological unresponsiveness or hyporesponsiveness (tolerance) can be induced by feeding protein antigens to naïve animals. Using a classical oral ovalbumin gut-induced tolerance protocol in BALB/c mice we investigated the effects of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on high-and low-dose oral tolerance (and in non-tolerised animals, i.e. effects of antigen challenge alone) in relation to lymphoproliferative, cytokine and antibody responses. Fish oil rich in long-chain n-3 fatty acids decreased both T-helper (Th) 1- and Th2-like responses. In contrast, borage (Borago officinalis) oil rich in n-6 PUFA, of which γ-linolenic acid is rapidly metabolised to longer-chain n-6 PUFA, increased Th1-like responses and decreased Th2-like responses, and possibly enhanced suppressor cell or Th3-like activity. These findings are in general agreement with other studies on the effects of long chain n-3 PUFA on immune system functions, and characterise important differences between long-chain n-3 and n-6 PUFA, defining more precisely and broadly the immunological regulatory mechanisms involved. They are also discussed in relation to autoimmune disease.

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Section: Metabolism and Immunobiology Of Polyunsaturated Fatty Acidssupporting

confidence: 73%

Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses

Harbige

Fisher

2001

Proc. Nutr. Soc.

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“…For example, autoantigen binding B cells (3) and autoreactive T helper (Th) cells (4) have been demonstrated in healthy subjects, and it is relatively easy to induce autoimmune disease in normal animals with self antigens in adjuvant (5). Furthermore, suppressor T cells (T.) with specificity for a variety of self antigens (6)(7)(8)(9)(10) have been found. At present, however, it remains unclear whether antigen-specific T, serve only as a fail-safe mechanism for maintenance of self-tolerance or whether they are involved in inductive events during ontogeny as well.…”

mentioning

confidence: 99%

A role for suppressor T cells in induction of self-tolerance.

Gibson¹,

Basten²,

Walker³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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The potential role of suppressor T cells (T.) in the Induction of self-tolerance was investigated by eliminating I-J+ cells during ontogeny (I-J antigens are encoded by the I-I subregion of the murine major histocompatibility complex). To achieve this, F1 mice were exposed to anti-I-J antibodies via the transplacental route by mating B1O.A(3R) females, preimmunized with B1O.A(5R) cells, with CBA males. At 6 weeks of age, the offspring were injected with rat erythrocytes (RRBC) to induce erythrocyte autoantibodies. By comparison with agematched controls, T,-depleted mice produced siicantly higher titers of autoantibody, whereas there was no difference in the antibody response of the two groups to the foreign determinants on the RRBC. The selective increase in autoantibody production was mirrored at the clonal level by the appearance of self-reactive B-cell hybridomas after fusion of RRBC-immune spleen cells with the NS-1 cell line. On the other hand, when helper cell function of RRBC-primed cells was measured in a T-cell proliferative assay, Ts depletion in utero resulted in enhanced T-cell activity to nonself (RRBC) but not to self (mouse erythrocyte) determinants. Thus, helper T cells recognizing nonself determinants on RRBC appeared to be responsible for activating self-specific B cells, presumably through linked recognition of different epitopes on mouse erythrocytes. Taken together, these findings indicate that elimination of I-J+ cells during ontogeny can lead to the appearance and activation of "forbidden" B-cell clones and points to a central role for Ts in induction as well as maintenance of self-tolerance.A precise understanding of autoimmunity depends on identification ofthe mechanisms responsible for the induction and maintenance of self-tolerance. Despite substantial advances made in delineating the events underlying the development of tolerance to foreign antigens, a consensus has yet to be reached concerning the cellular basis of self-tolerance. Protagonists of the clonal deletion theory (1) and its more recent modifications (2) base their arguments for a repertoirepurging mechanism on the exquisite sensitivity of immature lymphocytes (e.g., pre-B-cells) to physiological concentrations of antigen (2). On the other hand, there are a number of experimental observations that are not compatible with a simple deletion model of self-tolerance but rather implicate the existence of active suppressor mechanisms capable of inhibiting autoimmune responses. For example, autoantigen binding B cells (3) and autoreactive T helper (Th) cells (4) have been demonstrated in healthy subjects, and it is rela-

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“…However, preliminary evidence suggests that the infusion of Le-R serum into Le rats does not alter their susceptibility to EAE induction. Disease resistance in the Le-R rat may reflect an imbalance in a nonspecific suppressor cell population as has been reported in association with a canine demyelinating disease (20,21), or from hyperreactivity in populations of BP-specific suppressor cells, which have been identified in both protected and EAE-recovered Le rats (22)(23)(24)(25)(26). Further efforts to delineate more precisely the nature of EAE resistance in Le-R rats are currently in progress.…”

Section: Discussionmentioning

confidence: 86%

Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis.

Waxman¹,

Perryman²,

Hinrichs³

et al. 1981

The Journal of Experimental Medicine

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Clinical resistance to the induction of experimental allergic encephalomyelitis was observed in a closed colony of Lewis (designated Le-R) rats. Disease susceptibility in randomly bred animals appeared to increase with increasing age. In the small group of young Le-R rats, which were susceptible, disease onset was delayed, severity of symptoms was reduced, and duration of clinical signs was abbreviated compared to conventional Lewis rats. The severity of histologic neural tissue lesions correlated with clinical observations. Breeding experiments indicated that most Le-R rats were resistant to disease induction regardless of whether their ancestors had been selected for susceptibility or resistance. The F3 generation of resistant lineage was uniformly resistant at all ages tested. Virtually all (Lewis X Le-R)F1 rats of either sex were resistant when challenged at 7-8 wk of age indicating that resistance was a dominant autosomal trait. Approximately half of (F1 X Lewis) backcross rats developed paralytic EAE whereas one-fourth were entirely resistant, suggesting that disease resistance may be mediated by one or two genes. Le-R rats shared at least some of the Lewis rat major histocompatibility antigens. Resistance apparently did not reflect a nonspecific impairment of cellular immune responsiveness. Le-R rats, which had been challenged with myelin basic protein, developed antigen-reactive cells specific for basic protein or its encephalitogenic fragment. Spleen cells obtained from basic protein-sensitized Le-R rats did not adoptively transfer disease into Lewis rats. In contrast, spleen cells obtained from basic protein-sensitized Lewis rats readily transferred disease into both Lewis and Le-R recipients. These data suggest that disease resistance may be a result of an immunologic deficit (or suppressor cell activity) expressed during the differentiation of antigen-reactive cells into disease-inducing effector cells.

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Evidence for suppressor cells in Lewis rats' experimental allergic encephalomyelitis

Cited by 75 publications

References 33 publications

Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses

Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses

A role for suppressor T cells in induction of self-tolerance.

Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis.

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