Erythema multiforme lesions are associated with expression of a herpes simplex virus (HSV) gene and qualitative alterations in the HSV-specific T-cell response

A common form of erythema multiforme, herpes-associated erythema multiforme (HAEM), occurs following infection with herpes simplex virus (HSV). Here we report that HSV gene expression and the qualitative nature of the virus-specific T-cell responses are related to HAEM lesion development. Skin from HAEM lesions and 1–3 months healed HAEM lesional skin were positive for the viral DNA polymerase gene (Pol) by polymerase chain reaction. However, gene expression as determined by immunohistochemistry with Pol-specific antibody was seen only in HAEM lesions, suggesting that lesion development is associated with Pol gene expression. Similar HSV-specific T-cell lymphoproliferative responses were seen in peripheral blood mononuclear cells (PBMCs) from patients with acute or healed HAEM lesions or HSV lesions and from HSV-seropositive patients with unrelated inflammatory diseases. However, the T-cell receptor variable (Vβ ) chain repertoire of HSV-stimulated PBMCs obtained from HAEM lesions was altered; the prevalence of some families of variable chain (namely Vβ16 and Vβ19) was reduced, whereas the prevalence of others was increased (namely Vβ2 and Vβ7). Vβ2 cells were found in HAEM lesional skin positive for Pol antigen, suggesting that these cells home to viral antigen-positive skin.     

CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments to the skin of patients with erythema multiforme (HAEM)

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.     

Familial lymphocytic infiltration of the skin: histochemical and molecular analysis in three brothers

BACKGROUND: Lymphocytic infiltration of the skin (Jessner and Kanof) is a T cell pseudolymphoma characterized by the occurrence of recurrent asymptomatic papules and plaques and by a coat-sleeve-like perivascular lymphoid infiltrate. Rarely, familial cases have been reported. OBJECTIVES: Our study was performed to address the question of a genetic predisposition in a case of familial lymphocytic infiltration by histochemical and molecular analysis. RESULTS: We report on 3 brothers with typical clinical and histological features of Jessner's lymphocytic infiltration of the skin. Immunohistochemical analysis revealed a mixed lymphocytic infiltrate with a predominance of CD8+ T cells in all 3 patients. Molecular determination of T cell clonality by PCR-based GeneScan analysis of the T cell receptor (TCR)-gamma-chain showed oligoclonal, pseudomonoclonal or polyclonal TCR-gamma rearrangement patterns in lesional skin and in peripheral blood of all 3 brothers, while no common TCR idiotype was detected. CONCLUSION: Inherited deviations in TCR usage seem unlikely as a special cause of familial Jessner's lymphocytic infiltration of the skin; lack of clonality furthermore supports the notion that this variant of the disease is as true a pseudo-T-cell lymphoma as are the spontaneous cases.     

Increased T-cell receptor Vβ2 chain expression in skin homing lymphocytes in psoriasis

Studies have shown over-representation of certain T-cell receptor (TCR) Vbeta chains in lesional psoriatic skin, implying selection or expansion, possibly by bacterial superantigen. We investigated the pattern of TCR Vbeta chain usage in peripheral blood lymphocytes (PBL) bearing the skin homing receptor cutaneous lymphocyte associated antigen (CLA) in psoriasis patients. Results showed increased expression of TCR Vbeta2 in CLA-positive PBL in psoriasis patients (n = 15) compared with normals (n = 10); P < 0.002. As Vbeta2 is preferentially expressed by lymphocytes responding to certain bacterial superantigens, this study could possibly indicate a role for superantigens in the pathogenesis of psoriasis.     

T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation

Granuloma annulare is a common granulomatous infiltration of the skin of unknown etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and could find in all patients significant numbers of CD4-T cells. These cells showed a broad usage of the different T cell receptor Vbeta families and a rather unbiased repertoire when the complementary determining region 3 spectra were analyzed by the Immunoscope technique. Comparison with the peripheral blood mononuclear cell repertoire, however, identified in all patients few skin-specific expansions, which were for one patient also present in two distinct skin sites. Extensive sequence analysis of the complementary determining region 3 region confirmed the presence of a limited number of skin-specific expansions together with various nonspecific T cell infiltrations. Analysis of the intralesional cytokine expression revealed abundant production of interleukin-2, which was not dominant in granulomas from leprosy patients and was not reflected by the cytokine profile in peripheral blood mononuclear cells. These results demonstrate the capacity of the granulomatous response to recruit T cells in high numbers with only few clones expanding specifically. The high local production of interleukin-2 might thereby play an important role in the nonspecific attraction of T cells to the granulomatous site.     

High diversity of the T‐cell receptor repertoire of tumor‐infiltrating lymphocytes in basal cell carcinoma

Whether specific T‐cell clones are present in tumor infiltrating lymphocytes (TILs) in BCC is unknown. We employed deep sequencing of mRNA coding for the T‐cell receptor (TCR) chains α‐ and β to characterize the repertoire of TILs in BCC. V and J gene‐usage and CDR3 length were computed to determine the clonality of TCR and degree of overlap in TCR repertoires between skin resident T‐cells and TILs. We found high diversity of the TCR repertoire in BCC and control skin with random V‐J gene usage and similar CDR3‐length distribution. Lack of TCR repertoire restriction indicates absence of tumor‐specific TIL clones in BCC.     

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM): a viral disease with an autoimmune component

Erythema multiforme (EM) is a clinical conundrum the name of which reflects the broad morphological spectrum of the lesions. Molecular and immunologic evidence that herpes simplex virus (HSV) causes a subset of EM lesions [herpes-associated EM (HAEM)] is reviewed, and new data are presented which suggest that autoreactive T-cells triggered by virus infection play an important role in HAEM pathogenesis. Disease development begins with viral DNA fragmentation and the transport of the DNA fragments to distant skin sites by peripheral blood mononuclear cells (PBMCs). HSV genes within DNA fragments deposited on the skin [notably DNA polymerase (Pol)] are expressed, leading to recruitment of HSV-specific CD4+ Th1 cells that respond to viral antigens with production of interferon-gamma (IFN-gamma). This step initiates an inflammatory cascade that includes expression of IFN-gamma induced genes, increased sequestration of circulating leukocytes, monocytes and natural killer (NK) cells, and the recruitment of autoreactive T-cells generated by molecular mimicry or the release of cellular antigens from lysed cells. The PBMCs that pick up the HSV DNA [viz. macrophages or CD34+ Langerhans cells (LC) precursors], their ability to process it, the viral proteins expressed in the skin and the presence of epitopes shared with cellular proteins may determine whether a specific HSV episode is followed by HAEM development. Drug-associated EM (DIEM) is a mechanistically distinct EM subset that involves expression of tumor necrosis factor alpha (TNF-alpha) in lesional skin. It is our thesis that the polymerase chain reaction (PCR) assay for HSV DNA detection in lesional skin and staining with antibodies to IFN-gamma and TNF-alpha, are important criteria for the diagnosis of skin eruptions and improved patient management.     

Subcutaneous Panniculitis‐Like T‐Cell Lymphoma in Children: A Review of the Literature

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is a type of skin lymphoma. Pleomorphic T‐cells infiltrate the subcutaneous tissue and mimic lobular panniculitis. We report a case occurring in a 12‐year‐old Chinese boy who presented with multiple indolent erythematous subcutaneous nodules on both extremities without systemic symptoms. He had a protracted course of multiple erythematous subcutaneous nodules for 1 year and underwent biopsy of lesional skin for histology and T‐cell receptor (TCR) gene analysis. Histopathology showed infiltration of medium to large atypical pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. TCR gene rearrangement shows monoclonal rearrangements of the TCR β and γ chains. Immunophenotypic studies showed that CD3, CD4, and CD8 were strongly and diffusely positive in lesional cells and that CD56 was focally positive. In contrast, these cells were negative for CD20, CD30, and CD68. The combined morphology, characteristic histologic features, and positive T‐CR gene rearrangement supported a diagnosis of SPTCL. He is being treated with combination chemotherapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone.     

Stimulation of T cells by autologous mononuclear leukocytes and epidermal cells in psoriasis

Summary Based on reports suggesting aberrant cell-mediated immunity and altered infiltration of immunocompetent cells into the skin in psoriasis, we studied the stimulation of T cells by autologous non-T mononuclear leukocytes (autologous mixed lymphocyte reaction, AMLR) and by epidermal cells isolated from lesional and clinically uninvolved skin in psoriasis (autologous mixed epidermal cell lymphocyte reaction, AMECLR). Age- and sex-matched individuals served as controls. We found that the AMLR in psoriasis (n=11) was similar to that in healthy controls (n=16); furthermore, cell proliferation was alike in the presence of either 5% AB-serum or autologous serum. By contrast, while the AMECLR in healthy controls (n=9) resembled that in psoriatics employing epidermal cells from univolved skin, epidermal cells from lesional sites (n=10) induced a significantly higher proliferation of autologous T cells in the AMECLR (P<0.01). We conclude that the in vitro stimulation of T cells by non-T mononuclear leukocytes is normal in psoriasis and is not regulated by autologous serum. Lesional psoriatic epidermal cells, however, are more active in stimulating autologous T cell proliferation than cells from univolved psoriatic or normal epidermis.     

Evidence for restricted Vbeta usage in the leukemic phase of cutaneous T cell lymphoma

Antibodies directed against the beta chain of the T cell receptor (anti-Vbeta antibodies) are useful to identify the Vbeta repertoire of T cells in various diseases and to quantify numbers of Vbeta-bearing T cells. The goals of this study were to identify Vbeta+ cases of leukemic phase cutaneous T cell lymphoma (CTCL) and to compare the percentage of positive calls with other measures of blood tumor burden, i.e., lymphocyte subsets with a CD4+CD7- and CD4+CD26- phenotype and Sezary cell counts. Thirty-three of 49 (67%) cases of leukemic CTCL reacted with an anti-Vbeta antibody. When combined with reports from the literature, the frequency of Vbeta5 (probably Vbeta5.1) usage was relatively high when compared with Vbeta2 that is also frequently expressed by normal CD4+ T cells. The percentage of Vbeta+ cells correlated to the percentage of CD4+CD7- and CD4+CD26- cells for cases in which the neoplastic cells were deficient in expression of CD7 and CD26, respectively, but not the Sezary cell count. We hypothesize that the increased Vbeta5.1 usage in CTCL may be the result of depletion of Vbeta2 and other Vbeta-bearing T cells by staphylococcal superantigens prior to neoplastic transformation, resulting in a relative increase in the frequency of Vbeta5.1 usage in CTCL.     

HSV‐associated erythema multiforme in a patient after hematopoietic stem cell transplantation

Herpes simplex virus (HSV)–associated erythema multiforme (HAEM) is an acute and self‐limiting mucocutaneous hypersensitivity reaction triggered by herpes virus infections. We reported a patient with HAEM after hematopoietic stem cell transplantation (HSCT). A 55‐year‐old man received HSCT 7 months ago. He suffered from chronic graft versus host disease 4 months after HSCT and was treated with prednisone and tacrolimus. One week ago, he developed generalized macules with leukopenia. Dermatological examination revealed multiple iris‐like erythemas on his trunk and extremities. The skin lesions and leukopenia resolved upon anti‐HSV treatment.     

Antigen-independent expansion of T cells from psoriatic skin lesions: phenotypic characterization and antigen reactivity

The pathogenesis of psoriasis appears to depend on T cells, which have been proposed to mediate the disease through an autoimmune process. To test this hypothesis we have propagated four T-cell lines from biopsies of psoriatic skin lesions by antigen-independent methods. Flow cytometric immunophenotyping showed the lines to be composed mainly of CD4-positive, αβ-cell receptor (TCR)-positive cells, which secreted a cytokine profile suggestive of predominant T-helper type 1 (Th1) status. Analysis of TCR variable region (Vβ) usage revealed two- to eight-fold increases in the expression of certain Vβ species in lesional lines as compared with autologous peripheral blood mononuclear cells (PBMC), with the increased Vβ species being expressed on more than 5% of cells in two of the lines. Lines were also used to test for responses to a range of epidermal antigen preparations in the presence of irradiated autologous PBMC as antigen-presenting cells. The lines failed to proliferate in response to psoriatic lesional stratum corneum extracts, dispase-separated normal human epidermal extracts, and an epidermal keratin preparation before and after trypsinization, in spite of good proliferative responses to anti-CD3 which indicated that the lines were not anergic. In addition, the lines and PBMC from normal volunteers and the patients with psoriasis gave little or no response to recombinant streptococcal M protein. Thus, in spite of accumulating evidence for selective expansion of certain Vβ-expressing T cells in psoriatic lesions, epidermal autoantigens have not been identified by using a bioassay which depended largely on the proliferation of lesional CD4-positive cells. The role of streptococcal M protein, which bears some homology with epidermal keratin is also open to question, at least in chronic plaque psoriasis. Further work is therefore required to obtain direct evidence that autoimmune processes are important in the pathogenesis of chronic plaque psoriasis.     

TCR Vbeta expression in the small bowel of patients with dermatitis herpetiformis and gluten sensitive enteropathy. Limited expression in dermatitis herpetiformis and treated asymptomatic gluten sensitive enteropathy

Dermatitis herpetiformis (DH) is a blistering skin disease characterized by cutaneous deposits of IgA and an associated, most often asymptomatic, gluten sensitive enteropathy (GSE). Gluten sensitive enteropathy is also seen in patients that do not have skin disease or cutaneous IgA deposits, but do have significant gastrointestinal (GI) complaints. Patients with DH and with GSE without skin disease have similar small bowel morphologic changes and HLA associations and both the skin disease and the GI symptoms can be controlled by a gluten free diet. It is not known what factors allow almost all patients with DH to continue to eat gluten and not develop symptomatic gastrointestinal disease. We have examined the expression of the Vbeta T-cell receptor (TCR) in the small bowel of patients with DH (n=11) and of patients with both symptomatic (n=10) and asymptomatic (n=7) GSE without skin disease to determine if differences in the pattern of TCR Vbeta expression are associated with differences in the clinical manifestations of these diseases. TCR Vbeta expression was analyzed using RT-PCR from small bowel biopsies. Patients with DH and those with GSE without skin disease that were on a gluten free diet and asymptomatic were found to express 6.6 and 5.6 out of 20 Vbeta families respectively, with no single family preference. Examination of peripheral blood lymphocytes from these patients did not reveal any restriction of TCR Vbeta family expression. In contrast, patients with symptomatic GSE expressed 12.6 Vbeta families (P< 0.05), with no consistent preferential expression of any single Vbeta family between patients. Patients with DH, who are continuing to ingest wheat, show a more restricted pattern of TCR Vbeta utilization, similar to that of treated patients with GSE without skin disease, and significantly different from GSE without skin disease patients eating gluten. These findings suggest that the restricted nature of the TCR Vbeta expression may play a role in the different clinical manifestations of dermatitis herpetiformis and isolated gluten sensitive enteropathy.     

Identification of a commonly used CDR3 region of infiltrating T cells expressing Vbeta13 and Vbeta15 derived from psoriasis patients

Psoriasis is a common inflammatory skin disease that is thought to be mediated by activated T cells. In this study, the complementarity-determining region 3 (CDR3) in T cell receptors was examined for a common sequence motif among the T cells infiltrated in psoriatic lesional skin. A common specific CDR3 motif (Vbeta13-DWTSGV-Jbeta2.7) in lesions from psoriasis patients was identified by polymerase-chain-reaction-based spectratyping analysis and DNA sequencing. In addition, VDJ rearrangement with highly homologous amino acid composition in the CDR3 was observed in Vbeta15 of T cell receptors in lesions derived from psoriatic patients. Remarkably, T cell receptors containing the Vbeta13-DWTSGV-Jbeta2.7 were also found in the clinically normal skin from the psoriasis patients, which might seem to be responsible for the artificial production of psoriatic lesions. The identified CDR3 motif was highly expressed in cutaneous lymphocyte antigen (CLA+) cells of peripheral blood mononuclear cells from psoriasis patients compared with the expression in healthy individuals. This result showed that the infiltrated CLA+ T cells with the Vbeta13-DWTSGV-Jbeta2.7 motif in peripheral blood mononuclear cells from psoriasis patients might be involved in the development of psoriatic lesions. In addition, the results in this study suggest that the infiltrated T cells with the Vbeta13-DWTSGV-Jbeta2.7 motif in psoriatic lesions may be involved in the pathogenesis of psoriasis.     

T cells and mast cells as a major source of interleukin-13 in atopic dermatitis

BACKGROUND: Interleukin (IL)-13 is a T-cell-derived cytokine that shares several functions with IL-4, including the induction of immunoglobulin E synthesis. Recent studies suggest that cytokines expressed locally in the skin play several critical roles in atopic dermatitis (AD), however, little is known about the role of IL-13 in AD lesions. OBJECTIVES: The present study was designed to characterize the involvement of IL-13 in AD in the skin and peripheral blood mononuclear cells (PBMC). METHODS: Using lesional and nonlesional skin from adult AD patients and normal skin from healthy volunteers, we performed RT-PCR, in situ RT and immunostaining to determine the IL-13 expression at the mRNA and protein levels. The actual numbers of IL-13 expressing cells in biopsy specimens were counted under the microscope. IL-13 mRNA expression in PBMC from AD patients and healthy volunteers was examined by RT-PCR analysis. RESULTS: IL-13 mRNA expression was detected by RT-PCR in lesional and nonlesional skin and in PBMC from AD patients, but not in normal skin or PBMC from healthy volunteers. In AD lesional skin, numerous IL-13 mRNA-positive cells were demonstrated by in situ RT, and similar numbers of IL-13-positive cells were also detected immunohistochemically. Smaller numbers of IL-13-positive cells were observed in AD nonlesional skin and in normal skin. The differences in the numbers of IL-13-expressing cells between lesional and nonlesional skin were statistically significant. Double immunostaining revealed that IL-13 was produced in approximately 40% of T cells and 20% of mast cells in AD lesional skin, suggesting that T cells and mast cells are major sources of IL-13 in AD lesions. CONCLUSION: IL-13 may play a local as well as a systemic role in the development of AD lesions.     

Contrasting patterns of streptococcal superantigen-induced T-cell proliferation in guttate vs. chronic plaque psoriasis

BACKGROUND: Streptococcal infection is strongly associated with guttate psoriasis (GP) and may also exacerbate chronic plaque psoriasis (CPP), possibly through the release of superantigenic toxins. OBJECTIVES: To investigate superantigen-induced generation of cutaneous lymphocyte associated antigen (CLA) -positive lymphocytes in GP compared with CPP. METHODS: Peripheral blood lymphocyte (PBL) expression of CLA and T-cell receptor Vbeta chain was assessed in patients with CPP and with active and resolved GP. Expression of superantigen-reactive Vbeta families was compared with in vitro superantigen-induced peripheral blood mononuclear cell (PBMC) proliferation. RESULTS: Peripheral blood mononuclear cells from patients with active GP showed a twofold increased proliferation after stimulation with streptococcal pyogenic toxins A and streptococcal pyogenic toxins C compared with controls (P < 0.01), whereas the response to the staphylococcal toxins and mitogenic stimulation was the same in all groups. Peripheral blood lymphocytes (PBL) from patients with active GP showed increased use of the superantigen-reactive families Vbeta2 (P < 0.01) and Vbeta17 (P < 0.05), which was not evident in the other patient groups or controls. This pattern of Vbeta expression was only observed in CLA-positive T cells. Furthermore, there was a positive correlation between Vbeta2 expression and enhanced proliferation after stimulation with SPEA (r = 0.82, P < 0.01) and SPEC (r = 0.74, P < 0.05) in active GP. CONCLUSIONS: This study supports the concept that streptococcal infection precipitates acute GP at least in part through superantigen driven generation of Vbeta-restricted CLA-positive skin homing lymphocytes, whereas we could find no evidence for a similar mechanism occurring in the maintenance of stable CPP.     

Predominant usage of distinct T-cell receptor Vβ regions by epidermotropic T cells in psoriasis

Abstract To investigate the role of T cells in psoriasis, we analyzed the T-cell receptor (TCR) repertoire in peripheral blood lymphocytes (PBLs) and in skin lesions of 9 patients with chronic plaque-stage psoriasis by means of immunohistochemistry. An extended panel of monoclonal antibodies detecting 11 different V(3 families was employed in this study. In the peripheral blood, no predominant TCR Vβ expression was detected and interindividual differences were small. Skin-infiltrating T cells showed only marginal differences in the TCR Vβ usage when compared with PBLs. However, in 3 patients the intraepidermal infiltrate comprised up to 40% of T cells expressing a TCR Vβ region which was virtually absent in the peripheral blood and the dermal infiltrate. Thus, although the TCR Vβ usage of skin-infiltrating T cells showed little difference compared to PBLs, several cases exhibited a significant increase of epider-motrophie T cells using one particular Vβ region.     

T-cell receptor β variable region (Vβ) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders. We investigated the variable region (Vβ) of the T-cell receptor (TCR) repertoire in CTCL and compared it to the Vβ repertoire in normal and eczematous skin. We used a panel of 21 anti-Vβ antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13 Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL not classified). Six biopsies of normal skin and 6 of eczematous skin lesions served as controls. We determined the frequency of the Vβ in normal and inflamed skin and compared it to the percentage of the respective Vβ in the malignant clone of the CTCL patients. The percentage of the Vβ positive CD4+ cells in relation to the total number of T cells in normal skin and inflamed skin differed from the distribution of the Vβ families in the peripheral blood monoiiuclear cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%). We identified the following clones : 1 V03.1 (1 MF), 7 V05.1 (1 CD8+ CTCL.l CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V|36.7 (1 SS), 7 Vβ8.1/8.2 (2 CTCL not classified,! PLEO, 2 MF, 2 SS), 1 V012.1 (1 PLEO), 3 Vβl7.1 (2 CTCL not classified, 1 MF), 2 Vβ22.1 (1 CTCL not classified, 1 MF), 1 TCR8 (SS). The frequency of the malignant clone Vβ usage corresponded well to the repertoire of Vβ in eczematous skin but not to the repertoire in PBMC. In 6 patients, the malignant clone was mainly localized in the epidermis. In 17 cases, the clone-specific cells were distributed in epidermis and dermis equally. A retrospective analysis showed that preferential epidermal homing of the clone was associated with a non-aggressive clinical course. The Vβ usage of CTCL and eczema suggests a special cutaneous microenvironment which might be co-created by certain (bacterial?) superantigens. A preferential epidermal homing of the clone might have prognostic implications.     

Homogeneous epithelial gamma delta T cell repertoire of the skin is shaped through peripheral selection

In contrast to the T cell receptor (TCR) diversity of major alpha beta T cells in lymphoid tissues, epithelial T cells of the murine skin, called dendritic epidermal T cells (DETC), express exclusively an invariant gamma delta TCR. Fetal thymic precursors of DETC immigrate to the skin before birth, and in adult mice T cells expressing the canonical gamma delta TCR identical to that of DETC are not found in other lymphoid or epithelial tissues. Here, we show that DETC precursors migrate to the gut as well as to the skin during fetal periods, but preferentially survive and expand in the skin after birth. We propose that similar to the thymic selection of the diverse alpha beta T cell repertoire, 'peripheral selection' of the homogeneous epithelial gamma delta T cell repertoire may be mediated by TCR signaling upon the recognition of the self-ligand, because the ligand for the DETC TCR was expressed only in the skin.