Definition of POSITIVE SELECTION

Toufic Renno trenno at isrec-sun1.unil.ch
Tue Feb 1 16:13:16 EST 1994


Dr. Colin R.A. Hewitt (crah1 at leicester.ac.uk) wrote:
: Date:          31 Jan 1994 23:33:45 GMT
: From:          trenno at isrec-sun1.unil.ch (Toufic Renno)
: Reply-to:      trenno at isrec-sun1.unil.ch (Toufic Renno)
: To:            "bionet.immunology mail newsgroup" <bionet-news at daresbury.ac.uk>


: I'm afraid it's got to be twice on the pipe. 

: Involution of the thymus doesn't stop the generation of T cells that need "selecting". 
: This gets back to a discussion we had a few weeks ago. Namely: in the absence of a 
: fully functional thymus, where do all the new thymocytes (which are generated at the 
: same rate as before) get selected. This led to speculation about the thymic remnant 
: being active, and the possibility of peripheral mechanisms taking over but I still feel  
: the question remains open.


: Dr. Colin R.A. Hewitt
: University of Leicester/MRC
: Centre for Mechanisms of Human Toxicity
: Hodgkin Building
: PO Box 138
: Lancaster Rd
: LEICESTER
: LE1 9HN
: U.K.

: Phone +44 (0)533 525587
: Fax +44 (0)533 525616
: E-Mail crah1 at le.ac.uk.


Colin and I seem to be in agreement on the major point of the debate: the
fact that selectable T and B cells get generated AT THE SAME RATE (this
statement was actually capitalized in my original article, for emphasis) from
the progenitor pool regardless of prior negative selection. What I am not sure
of, is whether the absolute numbers of mature, CD3hi T cells that make it to
the periphery are the same before and after thymic involution. Is there data
that unequivocally makes this point?  

>in the absence of a fully functional thymus, where do all the new thymocytes
>(which are generated at the same rate as before) get selected.

In fact, I don't know that they get selected to the same extent as neonatal
thymocytes do. One study (Bogue et al., 1991, EMBO J. 10:3654) showed that the
neonatal and adult alpha/beta repertoires of mature SP thymocytes are
different in that there is a paucity of N nucleotide insertions in the
newborn repertoire, and that this paucity is exagerated by selection events
that occur in the thymus. Now this is not meant to imply that there is no
negative selection of thymocytes from adult animals.  It simply shows the 
complexity of the parameters one has to evaluate in order to find out
"whether", "where", and "what kind" of negative selection occurs in an adult
animal.  

Toufi



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