CD3-T cell receptor modulation is selectively induced in CD8 but not CD4 lymphocytes cultured in agar.
The CD3-T cell receptor (TcR) complex is central to the immune response. Upon binding by specific ligands, internalized CD3-TcR molecules increase, and either T cell response or unresponsiveness may ensue depending on the triggering conditions. Using semi-solid agar culture, we have shown previously that quiescent CD4 but not CD8 lymphocytes generate clonal colonies under phytohaemagglutinin stimulation. Here we have demonstrated that the agar induces selective CD3-TcR modulation in the CD8 and not in the CD4 subset. CD8 lymphocytes preactivated in liquid culture and recultured in agar with exogenous recombinant interleukin-2 generate colonies with a modulated CD3-TcR surface expression. The peptides composing the CD3-TcR complex are synthesized in CD8 colonies as well as in CD4; however, the CD3 gamma chain is phosphorylated at a higher level in CD8 colonies. A component of the agar polymer, absent in agarose, appears to be the ligand that induces differential CD3-TcR modulation in the CD8 subset. In contrast to agar culture, CD8 colonies can be derived from quiescent CD8 lymphocytes in agarose. These CD8 colonies express unmodulated CD-TcR. CD3-TcR modulation with anti-CD3 monoclonal antibody prior to culturing in agarose inhibits the colony formation. We conclude that given triggering conditions can result in both CD3-TcR modulation and inhibition of the proliferative response selectively in the CD8 lymphocyte subset and not in the CD4.
Oudrhiri
N
N
INSERM U91, Hôpital Henri Mondor, Créteil, France.
Farcet
J P
JP
Gourdin
M F
MF
M'Bemba
E
E
Gaulard
P
P
Katz
A
A
Divine
M
M
Galazka
A
A
Reyes
F
F
D000362:Agar / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017252:CD3 Complex; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003470:Culture Media; D015536:Down-Regulation; D006801:Humans; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D003470:Culture Media; D011948:Receptors, Antigen, T-Cell; D000362:Agar