scholarly journals T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2580-2586 ◽  
Author(s):  
BJ Nickoloff ◽  
FO Nestle ◽  
XG Zheng ◽  
LA Turka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Skin Diseases ◽  
Family Members ◽  
Chinese Hamster ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes

Abstract The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7–1 and B7–2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7–1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7–1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7–1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7–1 expression on lymphocytes, B7–3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7–1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

scholarly journals T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2580-2586 ◽  
Author(s):  
BJ Nickoloff ◽  
FO Nestle ◽  
XG Zheng ◽  
LA Turka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Skin Diseases ◽  
Family Members ◽  
Chinese Hamster ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes

The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7–1 and B7–2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7–1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7–1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7–1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7–1 expression on lymphocytes, B7–3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7–1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

scholarly journals A puzzling diagnosis: mycosis fungoides masquerading as pyoderma gangrenosum

2020 ◽  
Vol 6 (6) ◽  
pp. 784
Author(s):  
Neil K. Jairath ◽  
Ruple Jairath ◽  
Krislyn Porter ◽  
Jon C. Davis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Pyoderma Gangrenosum ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Inflammatory Cell Infiltrate ◽  
Clonal Proliferation ◽  
Positron Emission ◽  
Metastatic Involvement

<p class="abstract">Mycosis fungoides (MF) is a form of cutaneous T cell lymphoma that initially affects the epidermis, and is characterized by the clonal proliferation of mature cluster of differentiation (CD4)+T cells. We report a 73-year old male presenting with chin and right axillary skin lesions that had ulceration and granulating areas. Initial biopsy revealed mixed inflammatory cell infiltrate, which suggested an initial diagnosis of pyoderma gangrenosum. Despite treatment, the progressive worsening of the skin lesions prompted multiple repeat biopsies, which eventually revealed a predominance of T cells within the infiltrate. A T cell receptor rearrangement resulted in elevated monoclonal T cell populations, confirming a diagnosis of MF. Subsequent positron emission tomography (PET) scans revealed metastatic involvement of the disease, which ultimately led to the patient’s death. Clinical presentations of MF can mimic several different clinical entities, including pyoderma gangrenosum. This report highlights the importance of a multimodal approach to the diagnosis of unidentified skin lesions.</p>

scholarly journals Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3ζ, the Signaling Chain of the T-Cell Receptor Complex

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 585-594 ◽  
Author(s):  
Linda A. Trimble ◽  
Judy Lieberman
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Complex ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus ◽  
Specific Cytotoxicity

Although human immunodeficiency virus (HIV)-infected subjects without acquired immunodeficiency syndrome have a high frequency of HIV-specific CD8 T lymphocytes, freshly isolated lymphocytes frequently lack detectable HIV-specific cytotoxicity. However, this effector function becomes readily apparent after overnight culture. To investigate reasons for T-cell dysfunction, we analyzed T-cell expression of the cytolytic protease granzyme A and of CD3ζ, the signaling component of the T-cell receptor complex. An increased proportion of CD4 and CD8 T cells from HIV-infected donors contain granzyme A, consistent with the known increased frequency of activated T cells. In 28 HIV-infected donors with mild to advanced immunodeficiency, a substantial fraction of circulating T cells downmodulated CD3ζ (fraction of T cells expressing CD3ζ, 0.74 ± 0.16 v 1.01 ± 0.07 in healthy donors; P < .0000005). CD3ζ expression is downregulated more severely in CD8 than CD4 T cells, decreases early in infection, and correlates with declining CD4 counts and disease stage. CD3ζ expression increases over 6 to 16 hours of culture in an interleukin-2–dependent manner, coincident with restoration of viral-specific cytotoxicity. Impaired T-cell receptor signaling may help explain why HIV-specific cytotoxic T lymphocytes fail to control HIV replication.

scholarly journals Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexandria C Wells ◽  
Keith A Daniels ◽  
Constance C Angelou ◽  
Eric Fagerberg ◽  
Amy S Burnside ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Cell Responses

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses.

scholarly journals Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood of Patients With Primary Cutaneous T-Cell Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1636-1642 ◽  
Author(s):  
J. Marcus Muche ◽  
Ansgar Lukowsky ◽  
Khusru Asadullah ◽  
Sylke Gellrich ◽  
Wolfram Sterry
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Systemic Disease ◽  
Cell Receptor ◽  
Skin Lesions ◽  
T Cell Lymphomas ◽  
Gradient Gel Electrophoresis ◽  
Advanced Stages ◽  
Temperature Gradient Gel Electrophoresis

Abstract Clonal T cells have been demonstrated in skin lesions of all stages of cutaneous T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL stage at which dissemination of clonal cells into peripheral blood occurs. Although the multifocal occurrence of cutaneous CTCL lesions and T-cell recirculation suggest an early appearance of neoplastic cells in the blood, circulating clonal T cells have only been detected in advanced stages. We investigated their occurrence by a highly sensitive polymerase chain reaction (PCR) assay amplifying T-cell receptor γ rearrangements and subsequent heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the amplification products. Circulating clonal T cells were found in 26 of 45 patients with mycosis fungoides (MF ), six of seven with Sezary's syndrome (SS), 10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12 pleomorphic, and two of two unclassified CTCL patients. Except for the blood specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris, atopic dermatitis, and healthy volunteers) revealed polyclonal amplification products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and skin, identity of both clones was indicated by HD-TGGE and confirmed by sequencing six of these cases. We found an unexpected high frequency of identical clonal T cells in peripheral blood and skin of CTCL patients, including early stages of MF. This supports the concept of an early systemic disease in CTCL and raises new questions concerning the pathogenesis.

Flow Cytometric Detection of Neoplastic T Cells in Patients with Mycosis Fungoides Based on Levels of T-Cell Receptor Expression

1994 ◽  
Vol 102 (6) ◽  
pp. 856-860 ◽  
Author(s):  
Miroslaw Kuchnio ◽  
Edward A. Sausville ◽  
Elaine S. Jaffe ◽  
Timothy Greiner ◽  
Francine M. Foss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Expression ◽  
Flow Cytometric

scholarly journals The expression of CD26 and CD40 ligand is mutually exclusive in human T- cell non-Hodgkin's lymphomas/leukemias

Blood ◽  
1995 ◽  
Vol 86 (12) ◽  
pp. 4617-4626 ◽  
Author(s):  
A Carbone ◽  
A Gloghini ◽  
V Zagonel ◽  
D Aldinucci ◽  
V Gattei ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Cell Lines ◽  
Critical Role ◽  
Cd40 Ligand ◽  
T Cell Lymphomas ◽  
Human T Cell ◽  
Hodgkin's Lymphomas

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T- cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

scholarly journals Alterations in T-Cell Receptor Vβ Repertoire of CD4 and CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Children

2003 ◽  
Vol 10 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Monica Kharbanda ◽  
Thomas W. McCloskey ◽  
Rajendra Pahwa ◽  
Mei Sun ◽  
Savita Pahwa
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Chronic Phase ◽  
Cell Receptor ◽  
Cd8 T Lymphocytes ◽  
Immunodeficiency Virus

ABSTRACT Perturbations in the T-cell receptor (TCR) Vβ repertoire were assessed in the CD4 and CD8 T lymphocytes of human immunodeficiency virus (HIV)-infected children who were receiving therapy during the chronic phase of infection by flow cytometry (FC) and PCR analysis. By FC, representation of 21 TCR Vβ subfamilies was assessed for an increased or decreased percentage in CD4 and CD8 T cells, and by PCR, 22 TCR Vβ subfamilies of CD4 and CD8 T cells were analyzed by CDR3 spectratyping for perturbations and reduction in the number of peaks, loss of Gaussian distribution, or clonal dominance. The majority of the TCR Vβ subfamilies were examined by both methods and assessed for deviation from the norm by comparison with cord blood samples. The CD8-T-lymphocyte population exhibited more perturbations than the CD4 subset, and clonal dominance was present exclusively in CD8 T cells. Of the 55 total CD8-TCR Vβ families classified with clonal dominance by CDR3 spectratyping, only 18 of these exhibited increased expression by FC. Patients with high numbers of CD8-TCR Vβ families with decreased percentages had reduced percentages of total CD4 T cells. Increases in the number of CD4-TCR Vβ families with increased percentages showed a positive correlation with skewing. Overall, changes from normal were often discordant between the two methods. This study suggests that the assessment of HIV-induced alterations in TCR Vβ families at cellular and molecular levels yields different information and that our understanding of the immune response to HIV is still evolving.

Expression of T-Cell Receptor Antigens in Mycosis Fungoides and Inflammatory Skin Lesions

1989 ◽  
Vol 93 (1) ◽  
pp. 116-120 ◽  
Author(s):  
Sara A. Michie ◽  
Elizabeth A. Abel ◽  
Richard T. Hoppe ◽  
Roger A. Warnke ◽  
Gary S. Wood
Keyword(s):  
T Cell ◽  
Mycosis Fungoides ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Inflammatory Skin
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