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Related post: Our previous studies indicated that the thymus is able to induce tolerance to self antigens not only
by deletional mechanisms but also by clonal inactivation (anergy). Transfer of the nonresponsive
cells into hosts that lack the self antigen or into in vitro culture results in a reversal of the
nonresponsive state, indicating that antigen is required to maintain Buy Vigora this nondeletional form of in
vivo tolerance.
The mechanism responsible for commitment to the ap or yS lineage has also been approached
using TCR transgenic mice. If TCR-P transcriptional regulatory elements are Vigora 100 used to direct
expression of the TCRoB transgenes, yb Vigora 50 T cells do not appear. Instead, there appears a CD48"
cell bearing the TCR-ap transgenic receptor, but with the developmental, phenotypic, and
functional properties of y5 T cells. These results suggest that T cell functions ma>; be associated
with a specific lineage, irrespective Order Vigora of TCR usage. These findings have led to an investigation of
the role of TCR transcriptional regulatory elements in lineage development.
PHS 6040 (Rev 1/64)
6-8
J.& OOVEWMENT PRfJTING OFFICE:
DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT
PROJECT NUMBER
ZOl AI 00581-03 LCMI
PERIOD COVERED
October 1, 1991 to September 30, 1992
TITLE OF PROJECT (BO characters or /ass. Title must til on one line between the borders.)
T Cell Tolerance and Memory
PRINCIPAL INVESTIGATOR (List other professional personnel below the Pnncipal Investigator.) (Name, title, laboratory, and institute affiliation)
PI: Polly C.E. Matzinger Expert LCMI, NIAID
Others : Adriana Bonomo
Garrett Hisatake
Albert Bendelac
Visiting Fellow Generic Vigora LCMI, NIAID
Howard Hughes Scholar LCMI, NIAID
Visiting Associate LCMI, NIAID
COOPERATING UNITS (if any)
None
LAB/BRANCH
Laboratory of Cellular and Molecular Immunology
T Cell Tolerance Unit
INSTITUTE AND LOCATION
NIAID, NIH, Bethesda, Maryland 20892
TOTAL STAFF YEARS:
PROFESSIONAL:
CHECK APPROPRIATE BOX(ES)
n (a) Human subjects D (b) Human tissues
n {a1) Minors
D (a2) Interviews
B (c) Neither
SUMMARY OF V(/ORK (Use standard unreduced type. Do not exceed the space provided.)
We are studying various aspects of the birth, life and death of T cells. BIRTH-1)
For years scientists have looked for a self-renewing stem cell in the thymus and
failed to find one. We found that intact fetal thymuses, placed under the kidney
capsules of SCID mice, continued to produce T cells for at least 6 months. We are
now studying whether the loss of this stem cell activity seen in the older
experiments is due to age of the cells, the age and/or irradiated state of Vigora Online the
recipient thymus, or the in vitro purification treatments. 2) In the presence of
IL-7, the differentiation of ap, Vigora Oil but not 70 T cells is reversibly blocked in thymic
organ cultures. We hypothesize that the levels of this lymphokine may regulate the
rate at which a^ T cells are produced.
LIFE : 1) Using mice primed before or after thymectomy, we found that virgin Vigora Price mice can
only oe primed for about 5 months after thymectomy, but mice primed before
thymectomy respond for at least 4 months, at which time they still contain large
number of cells expressing a 'virgin' surface phenotype, among which are a large
number of Cheap Vigora functionally immunized CTL. 2J_ CTL to some Ags (usually viruses) do not
seem to need help from CD4 T cells while CTL to other ags, (usually cellular Vigora 100 Tablets Ags) ,
are strictly help dependent. We have postulated that CTL activation by dendritic
cells or activated APCs may bypass CD4 help & that some viruses may directly
activate APCs. To test this hypothesis, we have immunized animals Vigora Tablets with purified
dendritic cells under conditions where CD4 T cell help is limiting. We found that
this procedure worlts Buy Vigora Online in some cases & not in others & are now characterizing the
differences.
DEATH-1) We 'found that thymic epithelium (TE) induces tissue specific tolerance in
developing thymocytes & that this Vigora 5000 tolerance does not extend to skin specific
antigens. Yet an animal is tolerance of its own skin. We are ow determining whether
this particular skin antigen is found on bone marrow cells. If not, then one must
begin to ask how an individual is tolerant of its own skin. 2J_ By grafting 2 sets
of congenic fetal thytnuses into normal & SCID recipients, we Tound that the mature
thymic T cell population may contain up to 10% recirculating T cells, that the
recirculating population contains both activated & resting cells, with a rather
high proportion of yd cells. We are now testing whether the recirculating
population ever exists the thymus again and whether, during its thymic soiourn, it
IS activated or tolerized by antigens not expressed in the thymus m which it
matured.
PHy BU4U (Hev. b/«i!)
6-9
LABORATORY OF HOST DEFENSES
1992 Annual Report
Table of Contents
ZOl AI
Project Number
Summary
00155-17
00481-07
00521-05
00614-02
00615-02
00644-01
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