Mechanisms in Delayed Hypersensitivity

Jl, Turk

doi:10.1111/j.1346-8138.1978.tb01853.x

Cited by 18 publications

(25 citation statements)

References 11 publications

(10 reference statements)

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“…The process occurs with a defined sequence, proceeds for a finite time, and persists for at least 3 wk (17) . Since this study was carried out in the skin of lepromatous leprosy patients, it is possible that the underlying disease state and the preexisting cells infiltrating the dermis may influence the rate and extent of the process.…”

Section: Discussionmentioning

confidence: 99%

The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.

Kaplan

Laal

Sheftel

et al. 1988

The Journal of Experimental Medicine

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Leprosy is a chronic granulomatous disease of man caused by the intracellular bacterium Mycobacterium leprae (1) . The clinical manifestations of the disease range from single paucibacillary lesions (tuberculoid) to disseminated multibacillary involvement of almost the entire skin (lepromatous) . The polarity of the disease depends in large measure on the ability of the host to mount a cellular immune response to the infectious agent (reviewed in reference 2) . To study the mechanisms underlying these delayed-type cell-mediated reactions, we have selected the response to a purified protein derivative of tuberculin (PPD)' in skin of the naturally sensitized hosts . We have already commented on the stimulation of keratinocyte proliferation and the induction ofMHC class II antigen (3), the local production of macrophage-activating lymphokines, the induction and localization of y IP-10 (4), and the influence of the delayed-type hypersensitivity reaction on the distribution of T6+ Langerhans cells (5) . More recently we have reported that the cellular response to PPD leads to the clearance of M. leprae from the skin of lepromatous patients (6) .In these studies we now present a detailed temporal examination of an effective tuberculin reaction in the skin of patients with lepromatous leprosy and comment on the determinants associated with the disposal of M. leprae .Volume

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Section: Discussionmentioning

confidence: 99%

The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.

Kaplan

Laal

Sheftel

et al. 1988

The Journal of Experimental Medicine

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“…Measurements were made gently and rapidly and on the same relative region of the pinna across different animals and treatment groups. The immune reaction thus induced is characterized by swelling at the site of challenge, and by an infiltration of macrophages and lymphocytes into the epidermis and dermis (19,20). A positive correlation between the increase in pinna thickness and the ongoing immune response has been reported (21,22), and this method has been widely used to monitor cell-mediated immune responses in vivo (19,23).…”

Section: Induction Of Dthmentioning

confidence: 99%

Stress-induced enhancement of skin immune function: A role for γ interferon

Dhabhar

Satoskar

Bluethmann

et al. 2000

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

143

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Contrary to the widespread belief that stress is necessarily immunosuppressive, recent studies have shown that, under certain conditions, stress can induce a significant enhancement of a skin cellmediated immune response [delayed-type hypersensitivity (DTH) or contact hypersensitivity]. Adrenal stress hormones and a stressinduced trafficking of leukocytes from the blood to the skin have been identified as systemic mediators of this immunoenhancement. Because ␥ interferon (IFN␥) is an important cytokine mediator of DTH, the studies described here were designed to examine its role as a local mediator of the stress-induced enhancement of skin DTH. The effect of acute stress on skin DTH was examined in wild-type and IFN␥ receptor-deficient (IFN␥R؊͞؊) mice that had previously been sensitized with 2,4-dinitro-1-fluorobenzene. Acutely stressed wild-type mice showed a significantly larger DTH response than nonstressed mice. In contrast, IFN␥R؊͞؊ mice failed to show a stress-induced enhancement of skin DTH. Immunoneutralization of IFN␥ in wild-type mice significantly reduced the stress-induced enhancement of skin DTH. In addition, an inflammatory response induced by direct IFN␥ administration to the skin was significantly enhanced by acute stress. Our results suggest that IFN␥ is an important local mediator of a stress-induced enhancement of skin DTH. These studies are clinically relevant because, depending on the nature of the antigen, DTH reactions mediate numerous protective (e.g., resistance to viral, bacterial, parasitic, and fungal infections) or pathological (e.g., autoimmune reactions and contact sensitivity reactions such as that to poison ivy) immune responses.

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“…2b). In total, 8 biopsies were taken from different positive skin reaction sites of 7 healthy controls (HS2 (23), 10,13,15,16,17,18) and cultured with a cocktail of cytokines that allowed the outgrowth of T cells in vitro in the absence of any additional antigenic stimulants. 30 T cells ex-filtrated the tissue, expanded within 3-4 weeks and were tested for their specificity in a short-term proliferation assay.…”

Section: Skin Reactions To Intracutaneous Injection With Hpv16 E2 E6mentioning

confidence: 99%

“…11,12 Delayed Type IV hypersensitivity (DTH) reactions are used as a general measure of cell-mediated immunity in vivo. 13 A local inflammatory reaction (induration and erythema), orchestrated by activated cytokine releasing CD41 memory T cells, usually appears within 24-72 hr after intradermal injection of antigen. [14][15][16] Delayed-type hypersensitivity reactions have been used to demonstrate an encounter with pathogens (e.g., Mantoux Test), vaccineinduced immune responses, [17][18][19][20] and in particular to show HPVspecific immune responses in various animal models.…”

mentioning

confidence: 99%

Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia

Hende

Poelgeest

Hulst

et al. 2008

Intl Journal of Cancer

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We have tested the safety and feasibility of a synthetic long peptide-based HPV16-specific skin test to detect cellular immune responses to HPV16 E2, E6 and E7 in vivo. Women with cervical neoplasia (n 5 11) and healthy individuals (n 5 19) were intradermally challenged with 8 different pools of HPV16 E2, E6 and E7 peptides. The skin test was safe as the injections were perceived as mildly painful and no adverse events were observed. The majority of skin reactions appeared significantly earlier in HPV161 patients (<8 days) than in healthy subjects (8-25 days). The development of late skin reactions in healthy subjects was associated with the appearance of circulating HPV16-specific T cells and the infiltration of both HPV16-specific CD41 Th1/Th2 and CD81 T cells into the skin. These data show that the intradermal injection of pools of HPV16 synthetic long peptides is safe and results in the migration of HPV16-specific T cells into the skin as well as in an increase in the number of circulating HPV16-specific T cells. The use of this test to measure HPV16-specific immunity is currently tested in a low resource setting for the measurement of spontaneously induced T-cell responses as well as in our HPV16 vaccination trials for the detection of vaccine-induced immunity. ' 2008 Wiley-Liss, Inc.Key words: HPV16/delayed type hypersensitivity; cellular immunity; ELISPOT; skin testThe main cause of cervical carcinoma and cervical intraepithelial neoplasia (CIN) is a persistent infection with one of the highrisk, oncogenic human papilloma viruses.1,2 Anogenital infection with a high-risk HPV type is very common.3-5 The rate of incidence of infection is estimated to be 80-85% worldwide.6 Fortunately, the majority of infected subjects will clear the virus infection within a year 7,8 , and only a small proportion of women will become persistently infected and are at risk to develop HPVrelated malignancies.9,10 Cell-mediated immune responses play an important role in controlling HPV infections. 11,12Delayed Type IV hypersensitivity (DTH) reactions are used as a general measure of cell-mediated immunity in vivo.13 A local inflammatory reaction (induration and erythema), orchestrated by activated cytokine releasing CD41 memory T cells, usually appears within 24-72 hr after intradermal injection of antigen. [14][15][16] Delayed-type hypersensitivity reactions have been used to demonstrate an encounter with pathogens (e.g., Mantoux Test), vaccineinduced immune responses, [17][18][19][20] and in particular to show HPVspecific immune responses in various animal models.21-23 H€ opfl et al. were the first to study HPV16-specific cellular immunity by skin test in humans 24,25 and showed that a skin reaction, appearing within 2-6 days after intradermal injection with HPV16 E7, was correlated with regression of HPV-induced CIN lesions.We have previously studied the HPV16-specific T-cell responses in great detail in vitro, and the results of these studies suggested that the HPV16 E2, E6 and E7 specific Type 1 and Type 2 T-cell response ...

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Mechanisms in Delayed Hypersensitivity

Cited by 18 publications

References 11 publications

The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.

The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.

Stress-induced enhancement of skin immune function: A role for γ interferon

Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia

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