Cell‐mediated immune response to unrelated proteins and unspecific inflammation blocked by orally tolerated proteins

Ramos, Gustavo; Rodrigues, Claudiney Melquíades; Azevedo, Geraldo Magela de; Pinho, Vanessa; Carvalho, Celso Morato de; Vaz, Nelson M.

doi:10.1111/j.1365-2567.2008.02901.x

Cited by 19 publications

(19 citation statements)

References 33 publications

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“…These and previously published results 24,[27][28][29]31 show that the exposure to tolerated antigens under immunogenic conditions has broader (general) biological and medical significance through presently undefined systemic effects that interfere with a wide array of activities, among which the regeneration of skin lesions is an important target. As the inflammatory response in the early wound is thought to be primarily innate, the idea that indirect effects of oral tolerance within the adaptive system have an impact on wound healing is highly novel.…”

Section: Discussionsupporting

confidence: 54%

“…8,14 We have shown that the indirect effects of oral tolerance triggered by the exposure to tolerated antigens block inflammatory reactions, such as those produced by carrageenan or DTH, and inhibit polymorphonuclear and mononuclear leukocyte influx into peripheral tissues. 24,28 Here, we found that the indirect effects of oral tolerance reduce the initial process of inflammation after skin lesion. The total number of inflammatory cells in the healing area of tolerant mice was lower than that in control mice (Figure 2).…”

Section: Discussionmentioning

confidence: 80%

“…21,25,26 We have previously shown that the injection of ovalbumin (OVA) plus an adjuvant into mice that were orally tolerant to OVA triggers indirect effects that inhibit immune responses to unrelated antigens and blocks inflammatory reactions, such as delayed-type hypersensitivity (DTH) triggered by keyhole limpet hemocyanin, the formation of granulomas, and also paw edema triggered by carragenan. 27,28 These indirect effects of oral tolerance occur even when the tolerated antigen and the second unrelated antigen are injected into separate sites as well as with different orally tolerated antigens. 25,26 The indirect effects of oral tolerance do not require the simultaneous injection of the tolerated protein and the second antigen: it is still present 72 hours after an injection of the tolerated antigen, but does not occur if the tolerated protein is injected after the second antigen.…”

mentioning

confidence: 99%

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Indirect effects of oral tolerance improve wound healing in skin

Costa¹,

Ruiz-de-Souza²,

Azevedo³

et al. 2011

Wound Repair Regeneration

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Tissue injury in adult mammalian skin frequently results in scarring while fetal mammalian skin heals with complete regeneration. Inflammatory reactions are among the factors thought to impair regeneration. Previous studies have shown that the injection of an immunologically tolerated protein blocks immune responses to unrelated antigens and is also able to inhibit inflammation in mice. This phenomenon, which we refer to as the indirect effects of oral tolerance, does not require the simultaneous injection of the tolerated antigen and the second antigen, and also occurs when the two antigens are given by separate routes of immunization. Herein, we investigated whether the i.p. injection of an orally tolerated antigen (ovalbumin, OVA) would inhibit inflammatory reactions at an incisional lesion and influence healing of adult mouse skin. In OVA-tolerant mice, the injection of OVA minutes before wounding altered inflammation: it reduced the numbers of mast cells, neutrophils, and lymphocytes but increased the number of macrophages around the lesion area. Tolerant mice also showed fewer myofibroblasts and reduced scar area. Furthermore, tolerant mice displayed a pattern of extracellular matrix deposition similar to that observed in intact skin, plus characteristics of regeneration, such as an increased deposition of fibronectin and tenascin-C. These observations suggest that the indirect effects of oral tolerance can alter the process of wound healing in skin and reduce scar formation.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

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Indirect effects of oral tolerance improve wound healing in skin

Costa¹,

Ruiz-de-Souza²,

Azevedo³

et al. 2011

Wound Repair Regeneration

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“…Fluorescent images were acquired using the same exposure time. Myosin-specific autoantibodies were measured by indirect Elisa as previously described (61).…”

Section: Methodsmentioning

confidence: 99%

Myocardial aging as a T-cell–mediated phenomenon

Ramos

Berg²,

Silva

et al. 2017

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

145

117

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In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissueresident leukocytes and with an accumulation of activated CD4 + Foxp3 − (forkhead box P3) IFN-γ + T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.T he myocardial cellular composition has been revisited in recent years, and leukocyte subsets residing in the healthy heart have been described (1-10). Cardiac-resident macrophages exhibiting an M2-like gene expression profile were found to be distributed in close association with the coronary vascular bed (3), and niches for dendritic cells (CD11c + MHC-II high CD80/86 low ) were found near the cardiac valves of the intact heart (1). It was also demonstrated that cardiac-resident MHCII + cells process and present myosin heavy chain-alpha-derived peptides under steady-state conditions (11, 12) and prime T cells ex vivo (1). However, whether lymphocytes can seed the intact myocardium and whether T-cell priming with myocardial antigens can occur in the absence of an infection or autoimmune myocarditis remain elusive.More recently, accumulating evidence indicated that noninfectious myocardial diseases are modulated by T cells. During the last couple of years, our group demonstrated that ischemic, sterile myocardial injuries can elicit lymphocyte activation directed against cardiac antigens (13-16). Our previous data, showing for the first time that CD4 + T cells reactive to cardiac components can foster the healing process that takes place after myocardial infarction, were corroborated by several other reports (13,15,(17)(18)(19)(20). However, these autoreactive T cells can also b...

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“…Food allergy is generally interpreted as a failure of oral tolerance [4]; however, there is also evidence that oral tolerance, rather than being an inhibition, promotes a stabilization of immune responsiveness [11, 12] by directly modifying inflammatory reactions [13]. We suggest that prolonged restriction and voluntary ingestion of the specific antigen by immunized animals may hinder allergic reactions and may be reached with minor digestive disturbances.…”

Section: Introductionmentioning

confidence: 99%

Prolonged Antigen Ingestion by Sensitized Mice Ameliorates Airway Inflammation

et al. 2011

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Food allergy frequently precedes or coexists with respiratory allergy, and although restriction of contacts with the allergen is the elected clinical procedure, oral immunotherapy (OIT) has proven to be surprisingly efficient in clinical trials. We investigated whether prolonged restriction and voluntary exposure of previously sensitized (immunized) mice to ovalbumin (OVA) in the drinking water would alter subsequent responses to bronchial (aerosol) challenge with OVA. We found a significant suppression of bronchial inflammation, with marked reduction of eosinophils. IL-4, CCL-2, and CCL-11 are not associated with elevation in IL-10 production or Foxp3 expression, with only minor digestive symptoms.

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Cell‐mediated immune response to unrelated proteins and unspecific inflammation blocked by orally tolerated proteins

Cited by 19 publications

References 33 publications

Indirect effects of oral tolerance improve wound healing in skin

Indirect effects of oral tolerance improve wound healing in skin

Myocardial aging as a T-cell–mediated phenomenon

Prolonged Antigen Ingestion by Sensitized Mice Ameliorates Airway Inflammation

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