Human intestinal mucosa alters T-cell reactivities.
BACKGROUND
Compared with T cells in peripheral blood, lamina propria T lymphocytes have a low proliferative response to stimulation via the T-cell antigen receptor/CD3 complex or by protein kinase C activators yet largely preserve or even show an enhanced reactivity to CD2 and CD28 triggering. Coculture of peripheral blood T lymphocytes with intestinal mucosa supernatant leads to a similar functional behavior as found in freshly recovered lamina propria T lymphocytes. The aim of this study is to characterize the nature of substances in the mucosal supernatant responsible for downregulation of T-cell receptor-dependent signals.


METHODS
Mucosal supernatant was produced, dialyzed, digested with proteinase K, reduced by 2-mercaptoethanol or dithiothreitol, and tested for its activity on peripheral blood T lymphocytes.


RESULTS
Supernatant lost its activity after dialysis through a membrane (pore size 12,000-14,000). Digestion with proteinase K does not abolish its activity suggesting that the substances are neither proteins nor peptides. However, its effects on T lymphocyte proliferation can be reversed by reducing agents like 2-mercaptoethanol or dithiothreitol, suggesting that oxidative substances are contained in mucosal supernatants.


CONCLUSIONS
Our data support the view that mucosal substances that down-regulate antigen receptor-induced T lymphocyte proliferation are small, nonprotein, nonpeptide molecules with oxidative properties.
Qiao
L
L
German Cancer Research Center, Heidelberg.
Schürmann
G
G
Autschbach
F
F
Wallich
R
R
Meuer
S C
SC
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology; D018801:CD2 Antigens; D017252:CD3 Complex / Q000032:analysis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011493:Protein Kinase C