In article <Marc.Lavoie-1005972137350001 at poste19-206.bcm.ulaval.ca>,
Marc.Lavoie at bcm.ulaval.ca (Marc Lavoie) wrote:
> I would appreciate informations on the following subjects.
>> 1) Are T cells really matures when they leave the thymus? If yes, how to
> explain the induction of T cell anergy in periphery? It is generally
> imputed to the absence of a second signal given by antigen presenting
> cells. Could it be due to the absence of molecules in T cells which are
> only expressed or secreted after they leave the thymus. This could let the
> time to T cells directed against self antigens to encounter self antigens
> in periphery, and be functionnally inactivated or deleted. In this way
> only T cells directed agains non-self antigens would develop.
>> 2) I try to understand the mechanism of tolerance against indigenous
> bacteria. Is it more easy to induce oral tolerance at birth? Are
> indigenous bacteria when they colonize the digestive tract immidiatly
> after birth encounter a fully developed mucosal and systemic immune
> system?
>> Thanks in advance
>Dear Harold,
to 1: Yes, T cells are mature still in the thymus:
Wilson, A., L.M. Day, R. Scollay, and K. Shortman. 1988. Subpopulations of
mature murine thymocytes: properties of CD4-CD8+ and CD4+CD8-
thymocytes lacking the heat-stable antigen. Cell Immunol.117:312.
Chen, W.F., T. Ewing, R. Scollay, and K. Shortman. 1988. Growth of single T
cells and single thymocytes in a high cloning efficiency filler-cell free
microculture system. Thymus.12:51.
Dyall, R., and J. Nikolic-Zugic. 1995. The majority of postselection CD4+
single-positive thymocytes requires the thymus to produce long-lived,
functional T cells. J Exp Med.181:235.
Scollay, R., W.F. Chen, and K. Shortman. 1984. The functional capabilities
of cells leaving the thymus. J Immunol.132:25.
Dyall and Nikolic-Zugic actually show that thymocytes can mediate GvHD.
Further to your question, there are several mechanisms to explain
anergy induction in peripheral tissues. Apart from the 'sexy' second
signal, there is lack of help (e.g. Keene and Forman, J Exp Med 1982
155: 768; my paper 'nobody' cites: Kirberg, Bruno, and von Boehmer,
Eur J Immunol. 1993. 23: 1963 and find some more references there)
anergy by exhaustion (Moskophidis, Lechner, Pircher, and Zinkernagel,
1993 Nature, 362, 758-61.) and some 'stuff in between' depending
on antigenic dose (Rocha, Grandien, and Freitas, (1995).J Exp Med
181, 993-1003.).
to 2: someone else might start over ... ?
Ciao,
jorg
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