T Cells in Regenerating Feathers of Smyth Line Chickens with Vitiligo

Erf, Gisela F.; Trejo-Skalli, A.V.; Smyth, J. Robert

doi:10.1006/clin.1995.1105

Cited by 44 publications

(33 citation statements)

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“…Such an imbalance in CD4 to CD8 ratios was also reported in a study on the Smyth line chicken animal model for vitiligo, where CD8 ϩ T cells prevail after the onset of the depigmentation process (Erf et al, 1995). Furthermore, the presence of activated T cells in generalized vitiligo may be due to the preferential migration of skin-homing CLA ϩ T cells near target melanocytes.…”

Section: Figuresupporting

confidence: 63%

Local Immune Response in Skin of Generalized Vitiligo Patients

Wijngaard

Wańkowicz-Kalińska

Poole

et al. 2000

Laboratory Investigation

219

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SUMMARY:In situ immune infiltrates in lesional, perilesional, and nonlesional skin biopsies from patients with vitiligo were analyzed by immunohistochemistry and compared with immune infiltrates found in the skin of normal healthy donors and relevant disease controls. An increased influx of activated skin-homing T cells and macrophages were seen in the perilesional biopsies. The overall percentages of cutaneous leukocyte-associated antigen-positive (CLA ϩ ) T cells were similar to those found in normal healthy donors. This is compatible with the similar expression of E-selectin. Most strikingly, however, the CLA ϩ T cells in perilesional skin were mainly clustered in the vicinity of disappearing melanocytes, and 60% to 66% of these interacting T cells expressed perforin and granzyme-B. The perforin ϩ /granzyme-B ϩ cells were not seen in locations different from that of disappearing melanocytes. Interestingly, the majority of the infiltrating T cells were HLA-DR/CD8 ϩ . Another hallmark of the present study is the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in the epidermis at the site of interaction between the immune infiltrates and the disappearing melanocytes. The data presented in this study are consistent with a major role for skin-homing T cells in the death of melanocytes seen in vitiligo. (Lab Invest 2000, 80:1299-1309.

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Section: Figuresupporting

confidence: 63%

Local Immune Response in Skin of Generalized Vitiligo Patients

Wijngaard

Wańkowicz-Kalińska

Poole

et al. 2000

Laboratory Investigation

219

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“…It has been suggested that the vitiligo pathogenesis is similar in humans and animals. Indeed, antibodies against the pigmented cell surface antigens have been found in dogs, cats, and horses with vitiligo (8), and T cells infiltrating feather tissue are abundant before visible signs of vitiligo and in tissues undergoing active loss of pigment in Smyth chickens (9). Frequent combination of melanoma and vitiligo has been observed in Arabian horses and Sinclair swine (10), heralding regression or slow progression of the melanoma, but no relevant mouse model is currently available.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Vitiligo in an Animal Model for Human Melanoma

Lengagne

Gal²,

Garcette

et al. 2004

Cancer Research

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Tumor antigen-reactive T cells can be detected in a large proportion of melanoma patients, but their efficacy on tumor control in vivo remains unclear. On the other hand, vitiligo, a skin disorder characterized by patchy depigmented macules, may occur spontaneously or after antitumor therapies. Moreover, vitiligo is significantly associated with positive clinical response, but the mechanism is not understood. Therefore, the establishment of a relevant animal model in which melanoma and vitiligo spontaneously develop stepwise may be useful for better understanding of the parameters involved in the destruction of both benign and malignant melanocytes. In a previous work, we established a mouse model for melanoma in which MT/ret transgenic mice express the ret oncogene fused to the metallothionein promoter. Here we report that melanoma leads to spontaneous vitiligo. We further investigate, for the first time in this model, the natural antitumor T-cell response and evaluate the role of cellular immunity in the development of the disease. Interestingly, the occurrence of spontaneous tumor nodules in MT/ret mice with melanomaassociated vitiligo is significantly delayed when compared in melanoma mice without vitiligo. Moreover, a significant proportion of mice with melanoma-associated vitiligo resisted a challenge with syngeneic melanoma cells in contrast to animals without vitiligo. Our results confirm that vitiligo is associated with clinical benefit and further demonstrate the crucial role of CD8 ؉ T cells for tumor control in melanoma-associated vitiligo.

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“…Like in humans, an important role of CMI in the destruction of MC in SLV has been suggested by previous studies. Evidence supporting CMI as an effector mechanism in SLV includes the following observations: the loss of MC in feathers of SL chickens is always associated with large numbers of feather infiltrating lymphocytes composed predominantly of CD4+ and CD8+ T cells [25,26]; the ratio between feather infiltrating CD4+ cells and CD8+ cells, which was about 1.2 at visible onset of vitiligo, dropped to near 0.3 as a result of an increase in CD8+ cells during the progression of vitiligo [25,26]; and, vitiliginous SL chickens exhibit an in vivo CMI response to MHC-matched feather MC lysates [27]. These observations, together with a noted absence of inflammatory cells in the feather, suggest a role of cytotoxic T cellmediated mechanisms in MC death.…”

Section: Introductionmentioning

confidence: 99%