Selective Suppression of Delayed Hypersensitivity by the Induction of Immunologic Tolerance

Borel, Yves; Fauconnet, Marthe; Miescher, P. A.

doi:10.1084/jem.123.4.585

Cited by 42 publications

(14 citation statements)

References 14 publications

(11 reference statements)

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“…However, the exact relationship between these two immune responses is not well understood, although several laboratories have demonstrated that selective suppression of either delayed-type hypersensitivity or antibody formation can be achieved. For example, Asherson (8,9) and others (10)(11)(12)(13)(14)(15)(16) reported that animals pretreated with antigen in saline failed to develop delayed-type hypersensitivity to a subsequent challenge of the same antigen in adjuvant. In contrast there was a variable and usually slight effect on the antibody response.…”

Section: Discussionmentioning

confidence: 99%

Immune Response to Chemically Modified Flagellin

Parish

1971

The Journal of Experimental Medicine

171

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In the preceding paper (1) some chemical, antigenic, and biological properties of a series of acetoacetylated derivatives of Salmonella adelaide flagellin were described. Several chemical and antigenic tests revealed that as flagellin was acetoacetylated to increasing extents there was a steady decline in the affinity of the molecule for anti-flagellin antibodies. This loss in antigenic activity appeared to be accompanied on the one hand by a reduced capacity to initiate antibody formation but on the other hand b y an enhanced ability to induce antibody tolerance. In this paper the antibody tolerance induced by these acetoacetylated flagellins is studied in more detail. Furthermore, the ability of these acetoacetyl derivatives to induce delayed-type hypersensitivity is reported. F r o m these studies it was found that suppression of antibody formation in adult rats was accompanied by enhanced cell-mediated immunity. In fact, it appears that in adult animals antibody formation and cell-mediated immunity m a y well be opposing immunological processes. By contrast, tolerance induced in neonatal rats by acetoacetyl flagellin existed at the level of both humoral and cell-mediated immunity. Some preliminary aspects of this work have been reported elsewhere. 1 Materials and MethodsAnimals.--Randomly bred Wistar rats of either sex were used. Animals were either obtained directly from the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia, or bred in Canberra from Wistar breeders supplied by the Walter and Eliza Hall Institute. Both adult (6-10 wk of age) and neonatal rats were used.Antigens.--Flagellin and polymerized flagellin from S. adelaide (strain SW 1338; H antigen--fg) and flagellin from S. typhimurium (strain SL 871; H antigen--l, 2) were prepared as described previously (2). A cyanogen bromide (CNBr) digest of S. adelaide flagellin was prepared and fractionated into fragment A and a mixture of fragments B, C, and D as de-1 Parish, C. R. 1971. Suppression of antibody formation and concomitant enhancement of cell-mediated immunity by acetoacetylated derivatives of Salmonella flage]lin.

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Section: Discussionmentioning

confidence: 99%

Immune Response to Chemically Modified Flagellin

Parish

1971

The Journal of Experimental Medicine

171

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“…In contrast, there have been several reports of "immunological tolerance" occurring in adult animals at the level of both humoral and cell-mediated immunity (13,16,17,(19)(20)(21)(22)(23). However, in these systems complete tolerance was only induced by the administration of large quantities of antigen which was slowly eliminated and it would be expected that such antigen persisting in the serum would both desensitize delayed-type hypersensitivity and neutralize serum antibodies.…”

Section: Abilily Of Cyanogen Bromide-digested Flagellin To Induce Immmentioning

confidence: 99%

“…For example, it has been observed that "antibody tolerance" to tuberculin (12) and lysozyme (E. Benjamini, personal communication) in adult animals was accompanied by normal levels of delayed-type hypersensitivity. On the other hand, numerous investigators (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) have reported that pretreatment of adult animals with antigen in saline can suppress delayed hypersensitivity and this suppression is usually accompanied by "control" (13)(14)(15)(16)(17)(18)(19)(20)(21) and sometimes by heightened (22) levels of antibody.…”

Section: Abilily Of Cyanogen Bromide-digested Flagellin To Induce Immmentioning

confidence: 99%

Immune Response to Chemically Modified Flagellin

Parish

Liew

1972

The Journal of Experimental Medicine

177

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Recent studies in this laboratory have indicated that humoral and cell-mediated immunity may be intimately related (1-3). Using a series of acetoacetylated derivatives of flagellin, it was observed that increasing acetoacetylation steadily destroyed the ability of flagellin to initiate antibody formation but enhanced the capacity of the molecule to induce flagellin-specific delayed-type hypersensitivity and antibody tolerance. Thus, in this system antibody tolerance in adult rats was accompanied by enhanced cell-mediated immunity. If this relationship represents a general phenomenon, then it would be predicted that all states of antibody tolerance in adult animals should be accompanied by enhanced cell-mediated immunity. Using bacterial flagellin as the antigen, studies were initiated to test this prediction. I t has been previously reported that antibody tolerance to flagellin can be induced in adult rats by multiple injections of a cyanogen bromide (CNBr) digest of flagellin at two widely spaced dose levels (4). This phenomenon is called high and low zone antibody tolerance (5). Intermediate doses of the C N B r digest resulted in very high antibody titers rather than in antibody tolerance. D a t a presented in this paper reveal that, as predicted, both high and low zone antibody tolerance to flagellin were associated with heightened levels of delayed-type hypersensitivity. Furthermore, when enhancement of the antibody response occurred, suppression of delayed-type hypersensitivity was observed. Thus, an inverse relationship appears to exist between humoral and cell-mediated immunity. However, this relationship is not invariably true as rats from another strain exhibited only a partial inverse relationship. In addition, it was confirmed (3) that administration of antigen to neonatal rats induced tolerance at the level of both humoral and cell-mediated immunity. Materials and Methods Animals.---Outbred

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“…"Split tolerance' has also been demonstrated in non-obese diabetic mice receiving intrathymiĉ injection of glutamic acid decarboxylase 65 [15]. Furthermore, tolerance of T cells but not B cells has previously been identified after feeding [25 27] and injection [28][29][30][31] of low doses of antigen to animals. It is unlikely that the manipulation of intrathymic itijection of antigens leads to sueh selective unresponsiveness of Thi.…”

Section: Discussionmentioning

confidence: 82%

'Split tolerance’ induction by intrathymic injection of acetylcholine receptor in a rat model of autoimmune myasthenia gravis; implications for the design of specific immunotherapies

Ohtsuru

Matsuo

Fukudome

et al. 1995

Clinical and Experimental Immunology

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SUMMARYExperinienlal autoiinmune myasthenia gravis (EAMG) in ihe Lewis rat, induced by a single injection of acetyicholine receptor (AChR) protein, is a model used to study human myasthenia gravis (MG), The production of anti-AChR antibodies In the animal model and human MG is T cell-dependenl, and AChR-specific T cells have been considered as a potential target for specific immunotherapy. Intrathymic injection of antigens induces antigen-specific tolerance in several T cell-mediated autoimmune models. We examined the effect of intrathymic injection of AChR onT cell responses and the production of antibodies to AChR in EAMG rats. Primed lymph node cells from rats receiving intralhymic injection of AChR exhibited reduced proliferation to AChR with marked suppression of interferon-gamma (IFN--^) secretion in the antigen-stimulated culture, compared with those of rats injected with PBS. However, neither anii-Narke AChR nor anti-rat AChR antibody production was suppressed or enhanced in intrathymically AChR-injected animals compared with that of animals injected intrathymically with PBS or pcrithymically with AChR. This 'split tolerance" may be attributable to the suppression of type-1 T helper cells (Thi). Our results suggest that the suppression of Thi function alone may not be sufficient for the prevention of antibody-mediated autoimmune diseases.

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Selective Suppression of Delayed Hypersensitivity by the Induction of Immunologic Tolerance

Cited by 42 publications

References 14 publications

Immune Response to Chemically Modified Flagellin

Immune Response to Chemically Modified Flagellin

Immune Response to Chemically Modified Flagellin

'Split tolerance’ induction by intrathymic injection of acetylcholine receptor in a rat model of autoimmune myasthenia gravis; implications for the design of specific immunotherapies

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