Induction of murine T-helper-cell responses to the filarial nematode Brugia malayi

Pearlman, Eric; Hazlett, Fred E.; Boom, W. Henry; Kazura, James W.

doi:10.1128/iai.61.3.1105-1112.1993

Cited by 53 publications

(44 citation statements)

References 25 publications

(18 reference statements)

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“…Although this response could be modulated by IL-12, there was no effect on clearance of blood microfilaremia after i.v. injection (Pearlman et al 1995a). The current study demonstrates that IL-12 significantly down-modulates the physiological and immunological changes in the lung that are induced by B. malayi larvae, including airway eosinophilia, deposition of eosinophil granule proteins and tracheal hyperreactivity.…”

Section: Discussionmentioning

confidence: 54%

Interleukin‐12 suppresses filaria‐induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Mehlotra

Hall

Higgins

et al. 1998

Parasite Immunology

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Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-gamma, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology.

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Section: Discussionmentioning

confidence: 54%

Interleukin‐12 suppresses filaria‐induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Mehlotra

Hall

Higgins

et al. 1998

Parasite Immunology

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“…Several studies have demonstrated that reduced eosinophilia occurs when animals are given exogenous IL-12 during established Th-2 responses (Finkelman et al 1994, Wynn et al 1994, Pearlman et al 1995. However, when rIL-12 is given before a Th-2 response has been established, there is a more complete shift from Th-2 to Th-1 type responses.…”

Section: Discussionmentioning

confidence: 99%

IL‐12 eliminates the Th‐2 dependent protective immune response of mice to larval Strongyloides stercoralis

Rotman

Schnyder‐Candrian

Scott

et al. 1997

Parasite Immunology

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The goal of the present study was to determine if immune-mediated killing of S. stercoralis L3 in mice could be modulated by shifting from a Th-2 to a Th-1 type immune response. L3 killing in immunized mice was ablated in CD4+ T cell-depleted animals, but not in CD8+ T cell-depleted or beta 2-microglobulin-deficient mice. Treatment of immunized mice with IL-4 or IL-5 neutralizing MoAb significantly reduced the protective effects of vaccination against S. stercoralis, while protective immunity was unimpaired in IFN-gamma knockout mice. Recombinant IL-12 was administered to infected mice to switch the immune response from a Th-2 to a Th-1 type response. Protective immunity was ablated in immunized mice that received IL-12 therapy. Eosinophil numbers, eosinophil peroxidase levels, and parasite-specific IgG1 levels were lowered in IL-12 treated immunized animals, and parasite-specific IgG2a levels were increased in these animals. The data indicate that eosinophils are important as mediators of larval killing, and that the establishment of Th-2 type immunity results in killing of infective S. stercoralis L3, while a shift to Th-1 type immunity abrogates protective responses.

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“…Filters were dried and added to 5 ml scintillation fluid (EcoScint A; National Diagnostics, Inc., Manville, NJ), and the number of counts per minute was determined using a beta scintillation counter (Beckman Instruments, Fullerton, CA). Stimulation index was calculated as: cpm Ag stimulated/ cpm unstimulated (22).…”

mentioning

confidence: 99%

“…Measurements of IL-4, IL-5, and IFN-2* in culture supernarants were performed by two-site ELISA as described (22,25) using the following rnAbs: For IL-4, BVD6 was the coating and biotinylated BVD4 was the detecting mAb (obtained from Dr. F. Heinzel, Case Western Reserve University); for IL-5, TRFK5 was the trapping and TRFK4 was the detecting mAb (obtained from Dr. R. Coffman, DNAX, Palo Alto, CA); and for IFN-% R46A2 was the coating and XMG1.2 was the detecting mAb (obtained from American Type Culture Collection, Rockville, MD). Cytokines were measured after addition of streptavidinperoxidase and 0-phenylenediamine substrate (Sigma Chemical Co.), and absorbance was measured at 492 nm in a reader (Multiskan Plus MKII; Flow Laboratories, Inc., McLean, VA).…”

mentioning

confidence: 99%

Interleukin 4 and T helper type 2 cells are required for development of experimental onchocercal keratitis (river blindness).

Pearlman

Lass

Bardenstein

et al. 1995

The Journal of Experimental Medicine

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SummaryInflammation of the corneal stroma (stromal keratitis) is a serious complication of infection with the nematode parasite Onchocerca volvulus. Because stromal keratitis is believed to be immunologically mediated in humans, we used a murine model to examine the role ofT cells and T helper cell cytokines in the immunopathogenesis of these eye lesions. BALB/c mice immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens (OvAg) developed pronounced corneal opacification and neovascularization. The corneal stroma was edematous and contained numerous eosinophils and mononuclear cells. Strornal keratitis in immunized mice was determined to be T cell dependent based on the following observations: (a) T cell-deficient nude mice immunized and injected intrastromally with OvAg fail to develop corneal pathology; and (b) adoptive transfer of spleen cells from OvAg-immunized BALB/c mice to naive nude mice before intrastromal injection of OvAg results in development of keratitis. OvAg-stimulated lymph node and spleen cell cytokine production was dependent on CD4 cells and included interleukin (IL)-4 and IL-5, but not interferon % indicating a predominant T helper type 2 cell-like response. Inflamed corneas from immunized BALB/c mice and from reconstituted nude mice had greatly elevated CD4 and IL-4 gene expression compared with interferon ~/. Mice in which the IL-4 gene was disrupted failed to develop corneal disease, demonstrating that IL-4 is essential in the immunopathogenesis of O. volvulus-mediated stroreal keratitis.

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Induction of murine T-helper-cell responses to the filarial nematode Brugia malayi

Cited by 53 publications

References 25 publications

Interleukin‐12 suppresses filaria‐induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Interleukin‐12 suppresses filaria‐induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

IL‐12 eliminates the Th‐2 dependent protective immune response of mice to larval Strongyloides stercoralis

Interleukin 4 and T helper type 2 cells are required for development of experimental onchocercal keratitis (river blindness).

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