A unique phenotype of skin-associated lymphocytes in humans

Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites

Louis Picker, Sara A. Michie, Lusijah S. Rott, Eugene C. Butcher

Research output: Contribution to journalArticle

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Abstract

It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CDS+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-δ-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion moleculehigh, CD45Rlow putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA 452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5% of lymphocytes within the T-cell areas of these tissues expressed this entigen, whereas in inflammatory skin lesions (n = 16), 85% were HECA 452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among lymphocytes, the preferential expression of the HECA-452 determinant by cutaneous T cells supports the hypothesis that the skin constitutes a immunologically unique lymphoid tissue and suggests that this molecule may play a role in either lymphocyte homing to skin or in lymphocyte interactions with the epidermis.

Original languageEnglish (US)
Pages (from-to)1053-1068
Number of pages16
JournalAmerican Journal of Pathology
Volume136
Issue number5
StatePublished - May 1990
Externally publishedYes

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Epitopes
Lymphocytes
T-Lymphocytes
Phenotype
Skin
Peripheral T-Cell Lymphoma
Antigens
Blood Cells
Mycosis Fungoides
Lymphoid Tissue
T-Cell Lymphoma
Membrane Glycoproteins
Thymocytes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Mitogens
Epidermis
Population
Immune System
Inflammation
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

A unique phenotype of skin-associated lymphocytes in humans : Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. / Picker, Louis; Michie, Sara A.; Rott, Lusijah S.; Butcher, Eugene C.

In: American Journal of Pathology, Vol. 136, No. 5, 05.1990, p. 1053-1068.

Research output: Contribution to journalArticle

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title = "A unique phenotype of skin-associated lymphocytes in humans: Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites",
abstract = "It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16{\%} of peripheral blood T cells, including both CD4+ and CDS+ T cells (17{\%} and 11{\%} HECA-452+, respectively), as well as TCR-δ-bearing T cells (32{\%}+). Most thymocytes (99{\%}) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion moleculehigh, CD45Rlow putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA 452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5{\%} of lymphocytes within the T-cell areas of these tissues expressed this entigen, whereas in inflammatory skin lesions (n = 16), 85{\%} were HECA 452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among lymphocytes, the preferential expression of the HECA-452 determinant by cutaneous T cells supports the hypothesis that the skin constitutes a immunologically unique lymphoid tissue and suggests that this molecule may play a role in either lymphocyte homing to skin or in lymphocyte interactions with the epidermis.",
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T2 - Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites

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AU - Butcher, Eugene C.

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N2 - It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CDS+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-δ-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion moleculehigh, CD45Rlow putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA 452 antigen is not a conventional activation antigen because it was not upregulated with mitogen stimulation of peripheral blood T cells. Most significantly, among 54 diverse specimens of normal/reactive lymphoid tissues and sites of chronic inflammation, there was a clear association of lymphocyte HECA-452 expression and cutaneous location. In extracutaneous sites (n = 38) only about 5% of lymphocytes within the T-cell areas of these tissues expressed this entigen, whereas in inflammatory skin lesions (n = 16), 85% were HECA 452+. The association of HECA-452 expression and cutaneous location was also seen in a series of T-cell lymphomas. The malignant cells of 16 of 18 cases of epidermotropic (patch/plaque) stage mycosis fungoides were HECA-452+, as well as 2 of 7 nonmycosis fungoides peripheral T-cell lymphomas in skin. In contrast, this antigen was not expressed in thymic (lymphoblastic) lymphomas (n = 14), nonepidermotropic (tumor) stage mycosis fungoides (n = 5), and noncutaneous peripheral T-cell lymphomas (n = 15). Among lymphocytes, the preferential expression of the HECA-452 determinant by cutaneous T cells supports the hypothesis that the skin constitutes a immunologically unique lymphoid tissue and suggests that this molecule may play a role in either lymphocyte homing to skin or in lymphocyte interactions with the epidermis.

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