Thymic emigrants isolated by a new method possess unique phenotypic and functional properties

Chong Kil Lee, Kyungjae Kim, Lisbeth A. Welniak, William J Murphy, Kathrin Muegge, Scott K. Durum

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

T cells that emigrate from the thymus have primarily been studied in vivo using fluorescent dye injection of the thymus. This study examined the properties of thymocytes that emigrate from cultured thymic lobes in organ culture. Under these conditions, thymic emigrants displayed the expected phenotype, that of mature thymocytes expressing high levels of T-cell receptor (TCR-αβ) and either CD4 or CD8, and were observed to emigrate within 24 hours of positive selection. Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium difficile toxin B, implicating active motility process. Most of the surface markers on αβ-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, α4-integrin, α5-integrin, CD45, and CD28) were expressed at a surface density similar to that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous expression of L-selectin and heat-stable antigen (HSA) suggested that subsets emerge from the thymus with a commitment to different migration patterns. The only marker on emigrants not found on either intrathymic cells or mature spleen T cells was CTLA-4, which could dampen the response of emigrants to peripheral antigens. Antigen responsivenes measured in vitro against allogeneic dendritic cells showed a proliferative response comparable to that of splenic T cells. In vivo, however, thymic emigrants failed to induce an acute graft-versus-host reaction in allogeneic severe combined immunodeficiency recipients. This suggests that a mechanism operating in vivo, perhaps tolerance or migration pattern, attenuates the response of emigrants against antigens that did not induce their deletion in the thymus.

Original languageEnglish (US)
Pages (from-to)1360-1369
Number of pages10
JournalBlood
Volume97
Issue number5
DOIs
StatePublished - Mar 1 2001
Externally publishedYes

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Thymus
T-cells
Antigens
Thymus Gland
T-Lymphocytes
Graft vs. host reactions
Integrins
Thymocytes
L-Selectin
Cytochalasin D
Pertussis Toxin
Severe Combined Immunodeficiency
Intercellular Adhesion Molecule-1
T-Cell Antigen Receptor
Fluorescent Dyes
Organ Culture Techniques
Emigration and Immigration
HLA Antigens
Dendritic Cells
Spleen

ASJC Scopus subject areas

  • Hematology

Cite this

Thymic emigrants isolated by a new method possess unique phenotypic and functional properties. / Lee, Chong Kil; Kim, Kyungjae; Welniak, Lisbeth A.; Murphy, William J; Muegge, Kathrin; Durum, Scott K.

In: Blood, Vol. 97, No. 5, 01.03.2001, p. 1360-1369.

Research output: Contribution to journalArticle

Lee, Chong Kil ; Kim, Kyungjae ; Welniak, Lisbeth A. ; Murphy, William J ; Muegge, Kathrin ; Durum, Scott K. / Thymic emigrants isolated by a new method possess unique phenotypic and functional properties. In: Blood. 2001 ; Vol. 97, No. 5. pp. 1360-1369.
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abstract = "T cells that emigrate from the thymus have primarily been studied in vivo using fluorescent dye injection of the thymus. This study examined the properties of thymocytes that emigrate from cultured thymic lobes in organ culture. Under these conditions, thymic emigrants displayed the expected phenotype, that of mature thymocytes expressing high levels of T-cell receptor (TCR-αβ) and either CD4 or CD8, and were observed to emigrate within 24 hours of positive selection. Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium difficile toxin B, implicating active motility process. Most of the surface markers on αβ-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, α4-integrin, α5-integrin, CD45, and CD28) were expressed at a surface density similar to that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous expression of L-selectin and heat-stable antigen (HSA) suggested that subsets emerge from the thymus with a commitment to different migration patterns. The only marker on emigrants not found on either intrathymic cells or mature spleen T cells was CTLA-4, which could dampen the response of emigrants to peripheral antigens. Antigen responsivenes measured in vitro against allogeneic dendritic cells showed a proliferative response comparable to that of splenic T cells. In vivo, however, thymic emigrants failed to induce an acute graft-versus-host reaction in allogeneic severe combined immunodeficiency recipients. This suggests that a mechanism operating in vivo, perhaps tolerance or migration pattern, attenuates the response of emigrants against antigens that did not induce their deletion in the thymus.",
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