Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 974-990
Upregulated Expression of Fibronectin Receptors Underlines the
Adhesive Capability of Thymocytes to Thymic Epithelial Cells During the
Early Stages of Differentiation: Lessons From Sublethally Irradiated
Mice
Sergio R. Dalmau,
Claudia S. Freitas, and
Wilson Savino
From the Program of Experimental Medicine, Basic Research Center,
National Cancer Institute, Rio de Janeiro, Brazil; the Department of
Biochemistry, Biology Institute, University of the State of Rio de
Janeiro, Rio de Janeiro, Brazil; and Laboratory on Thymus Research, the
Department of Immunology, Oswaldo Cruz Institute-Oswaldo Cruz
Foundation, Rio de Janeiro, Brazil.
A 250-cGy whole-body 
-radiation dose was used to induce thymus
regression in mice, and to study the expression and function of
extracellular matrix (ECM) receptors in distinct thymocyte subsets
emerging during repopulation of the organ. The onset of regeneration
was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable
increase in the absolute counts of
CD3
CD25hiCD44+ and
CD3CD25in/hiCD44
cells occurred. Enhanced expression of L-selectin, 
4, and 5 integrin chains (L-selhi 4hi
5hi) was also exhibited by these cells. This pattern of
expression was maintained until the
CD4+CD8+ (DP) young stage was achieved.
Afterward, there was a general downregulation of these ECM receptors in
DP as well as in CD4+ or CD8+ single
positive (SP) thymocytes (L-selin 4in
5in). In some recently generated SP cells, 4
expression was downregulated before the 5 chain, and L-selectin was
upregulated in half of more mature cells. The expression of the 6
integrin chain was downregulated only in maturing CD4+
cells. Importantly, the increased expression of L-selectin and 4 and
5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC
segment of fibronectin is targeted by the 4 integrin during
thymocyte/TEC adhesion; (2) that the RGD motif of the
120-kD fragment of fibronectin, a target for 5
integrin, has a secondary role in this adhesion; and (3) that the YIGSR
cell attachment motif of the 
1 chain of laminin/merosin recognized
by a nonintegrin receptor is not used for thymocyte adherence. In
conclusion, our results show that an upregulated set of receptors
endows CD25+ precursors and cells up to the young DP
stage with a high capability of interacting with thymic ECM components.
