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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1360-1369
IMMUNOBIOLOGY
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, and
Scott K. Durum
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-  ) 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 an active
motility process. Most of the surface markers on -thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, 4-integrin,
5-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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