Trapped in the medullary model

negatively

selected

partners.

Put another

obviously

dictated

by the data

available.

way, no particular VP-defined CDd- SP cells could hi distinguished based upon cell-cycle b lile. I also favour a local

Therefore, as the authors of each article suggest, since we do not have all the facts, the only way to resolve this dilemma is by more

‘lymphokine’ to explain these observations.

experimentation.

I read with interest the two recent Viezupoint

Even though neonatal SP cells contir, ue to

articles relating to thymic migration’,‘; both

proliferate in the presence of interleu kin 2 (IL-2) and/or IL-7 in &ro, I am still sceptical

that the thymic medulla of adult animals contains at least three populations of ‘ma-

raise important comment.

issues that are worthy

First, the technique

of

of labelling

thymocytes

directly

thiocyanate

(FITC) and looking for the ap-

with fluorescein

iso-

pearance of labelled cells in the periphery is designed

to look at the movement

of cells

from the thymus to the periphery. However,

as to the roles of these cytokines

in the pro-

ture’ cells: (1) freshly derived cells from the cortex; (2) recirculating peripheral T cells;

liferation of neonatal SP cells in z~izn Com-

and (3) locally generated cells responding

parison of the phenotypic profiles of SP cells in the neonate versus those in the adult

environmental antigens. Thus, the schematic model developed will be dictated by one’s

have been made (R. Ceredig, unpublished)

concept of the thymus medulla.

be carried out. In parenthesis,

mus will also be labelled by this technique.

cells in fetal thymic organ culture (FTOC)

1NSERIvl U-181,

By contrast, bromodeoxyuridine

are assumed

CNRS-LGME,

labels all dividing cells irrespective

of site.

to represent

those developing

although SP

cells similar to

irz ~livo,their phenotype

is

Rhodri Ceredig

lizstifut

dr Clzinzk Biolojjqffe,

Thus, in both these studies, is it certain that

very atypical; they are larger in size” and ex-

11 we Hwiu-irm,

thymocytes are the only cells measured, and

press more CD44 than their ilz ~izlucounter-

67085 Stimbozrrg,

n& either extrathymically

parts !R. Ceredig, unpublished). Does the cycling activity of neonatal thy-

F7lUlCtT.

cells traversing

derived T cells or

the thymus? Second, is ex-

pression of heat stable antigen (HSA) a reli-

mocytes serve any physiological

able marker for the degree of maturation of

My favoured

thymocytes?

that because cell cycling inhibits the func-

Epitopes

for anti-HSA

anti-

bodies are probably on the polysaccharide side-chains

of the small

could surface phenotype

HSA molecule;

rapidly switch?

adequately

considered

the developmental

reality of thymopoiesis. produces

The fetal +hymus

the first ‘mature’ single-positive

(SP) cells at day 18 for CD4’ cells3 and day 19 for CDS’ cells”. Since the thymus

immunological

relevance?

hypothesis

is

tional activity of the recombinase-activating gene (TUG-2) proteinlO, neonatal SP cells may be less !ikelvs either to ur,rlergo or to

Technical issues aside, neither article has

im-

References 1 Scollay, R. and Godfrey, D.1 (199% 11~zw~~uo1. To@/ 16, 268-273 2

Tough, D.F. and Sprent, J. (1995) Znz~~~zrual.

7?1dny16, 273-274 3 Ceredig, R., Dialy--as, D.P., Fitch, F.W. and MacDonald,

H.R. (1483) I. Esp. A&d. 158,

have undergone secondary rearrangements of the T-cell receptor (TCR) CY chain. This hy-

1654-l 671

pothesis

5 Ceredig, R. (1990) lut. Zn~~~~rr~ol. 2, 859-867

tional

predicts

a differerence

repertoire

between

in func-

neonatal

and

1 Ceredig, R. (1979) ~,7rllplrlrita~it,I;28, 377-381 6 Lawetzky, A., Kubbies, M. and Hiinig, T.

adult SP thymocytes. In the context of mice

(1991) Eli,: 1. b~zii~unol.21, 2599-2601

transgenic

7 Fisher, A.G. and Ceredig, R. (1991) 11zf.

for the male-specific

TCR recep-

mediately exports these cells, the “corveyor

tor (anti-H-Y), perhaps the delay in positive

bn~iuuzol. 3, 1323-1328

belt’ model is not [alid at birth. Although

selection

8 Ceredig, R. and Waltzinger, C. (1990) Int.

arguments

spite the apparent

are made that the neonatal pe-

until the postnatal

period”,

presence

de-

of both func-

riod is ‘exceptional’, unifying models have

tional ligand and negative selection in the

to accommodate

late embryo, is partly due to the postnatal

all data. CD4’ (and CD8’)

117217271m71. 2, 868-877

9 Ceredig, R. (1988) 1. I77777~7177d. 141, 355-362 IO

Lin, W-C. and Desiderio, S. (1995)

7ihy

appearance

rats6 are in cycle. This observation

van Boehmer, H. and Kisielow, l? (1990) De?.

true for cells in the yiS lineage’. In addition, T cells in she spleen of one-day-old mice are

TCR (Ychains. The stringency of negative selection in the late fetal and neonatal thymus of TCRs

12 Schneider, R., Lees, R., Pedrazzini, T.,

also in cycle (R. Ceredig, unpublished),

but

clearly different

whether

de-

This probably

such cells are all thymically

of cells expressing

recognizing

endogenous

I77~777777d.

16, 279-289

SP cells in the neonatal thymus of mice5 and is also

superantigens

liferation of SP cells in the neonate is prob-

ventional

ably antigen independent,

tielay in the expression of self-antigen

selection’

to account

for this. What we

is

a developmental

delay in superantigen

Sprent’ allude to a ‘slow form of negative

11 Teh, H.S., Kishi, H., Scott, B., Borgulya, l’.,

from that in the adult”. reflects

rived is unclear. I would agree that the proand Tough and

expression.

(self) antigens,

For con-

Zinkernagel,

R.M., Hengartner,

MacDonald,

H.R. (19891]. E-X/~. Med. 169,

may

Todw,

going negative selection in the neonatal thy-

plains

mus was indistinguishable

However,

available

data

H. and

2149-2158

also alter the rules of TCR selection. Returning to the articles in IIUIIZW~~J~~J~_I~

activity of VP-defined CD4’ SP cells underfrom their non-

z7?7777lr77ol. 1, l-10

developmental

I would acknowledge that attempting to develop a unifying model that ex-

showed in our study8 was that the cell-cycle

to

and I agree that additional analyses should

circulating T cells passing through the thy(BrdUrd)

Finally, I would speculate

is commendable.

the concept of scientific truth is

of 400 words of less can now be sent electronically to: [email protected] Correspondence