Specificity and Function of Clonally Developing T Cells

306 Pages·1986·20.343 MB·English

by  R. Scollay (auth.), Bernhard Fleischer M.D., Jörg Reimann M.D., Hermann Wagner M.D. (eds.)

Current Topics in
Microbiology
126 and Immunology
Editors
A Clarke, ParkvillelVictoria . R W. Compans,
Birmingham!A labama . M Cooper, BirmingbamlA labama
H. Eisen, Paris . W. Goebel, Wiirzburg . H. Koprowski,
Philadelphia . F. Melchers, Basel . M Oldstone,
La Jolla/California . R Rott, GieSen . P.K. Vogt, Los Angeles
H. Wagner, Ulm . I. Wilson, La Jolla/California
Specificity and
Function of Clonally
Developing T Cells
Edited by B. Fleischer, J. Reimann,
and H. Wagner
With 60 Figures
Springer-Verlag
Berlin Heidelberg New York Tokyo
BERNHARD FLEISCHER, M.D.
JORG REIMANN, M.D.
HERMANN WAGNER, M.D.
Department of Medical Microbiology and Immunology
University ofUlm
Oberer Eselsberg
D-7900Ulm
ISBN-13:978-3-642-71154-1 e-ISBN-13:978-3-642-71152-7
DOl: 10.1007/978-3-642-71152-7
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Softcover reprint of the hardcover 15t edition 1986
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Preface
The international workshop on "Specificity and Function
of Clonally Developing T Cells" was held at SchloG Rei
sensburg (near UIm, West Germany) on March 17-20,
1985. The meeting brought together immunologists study
ing clonal T-cell development in man and mouse in various
in vitro systems at the cellular as well as molecular level.
It was an attempt to provide an overview of the current
research interests of groups working on (a) the developmen
tal potential of in vitro expanding primary T-cell clones
(investigated using limiting dilution analysis) and cloned
T -cell lines established in long-term culture ; (b) the signals
required for the expression of particular patterns of (func
tional and antigen receptor) phenotypes by T cells which
are either freshly explanted in vitro, or maintained in vitro
as cloned long-term lines; and (c) the generation of an
MHC-restricted T-cell repertoire.
In the study of thymocytes emphasis has shifted towards
the presumably immature adult/embryonic subset(s) which
is (are) devoid of subset-specific differentiation markers
(L3T4, Lyt-2). Neither the signal requirement(s) for clonal
expansion in vitro of these cells, nor their precursor role
for any functional T -cell lineage are as yet unambiguously
established. The multiple modes of human T-cell activation
(e.g., via Tp44, T11, T3/Ti molecular complexes) were em
phasized by a number of presentations and raised the ques
tion of whether these different modes of activation induce
different functional activities in individual T-cell clones.
The fact that two or more different functional phenotypes
(e.g., helper and/or cytotoxic activity) can be activated in
many human T-cell clones established in long-term culture
raised the fundamental question of whether distinct T-cell
lineages irreversibly committed to the expression of a par
ticular pattern offunctional phenotypes do exist, or alterna
tively whether every individual T-cell clone is multipotential
with respect to the patterns of functional phenotypes it
can express, with environmental influences deciding on the
functional activity actually realized.
VI Preface
The sessions on the generation of T-cell receptor diversity
addressed three topics central to the issue. (a) The role
of somatic diversification in generating the T-cell receptor
diversity was discussed. In contrast to the B-cell system,
the available experimental evidence for a somatic diversifi
cation of the T-cell repertoire is preliminary. (b) The ques
tion of the self/nonself discrimination of the T-cell receptor
repertoire has become more complex, as the difference be
tween" physiologic self-reactivity" and" autoimmune reac
tivity" has become exceedingly difficult to define. The pres
ence of self-reactive T-cell clones in the intact immune sys
tem was acknowledged, but its functional significance re
mains controversial. (c) The role of MHC determinants
in "guiding" the generation of diversity of the T-cell reper
toire was discussed with reference to the two previous top
ics. New data on allorestricted T-cell repertoire develop
ment in vitro raised basic questions on the role of MHC
structures in directing the process of unfolding of the T-cell
repertoire.
We are grateful for support from the Deutsche For
schungsgemeinschaft and indebted to Springer Verlag, for
its interest in editing and publishing these proceedings.
UIm, Spring 1986 HERMANN WAGNER
BERNHARD FLEISCHER
JORG REIMANN
Table of Contents
Part A: Development of T Lymphocytes in the
Thymus
R. SCOLLAY: Introductory Remarks 3
K. SHORTMAN, R. SCOLLAY, P. ANDREWS, and R.
BoYD: Development of T Lymphocytes Within the
Thymus and Within Thymic Nurse Cells. With
3 Figures . . . . . . . . . . . . . 5
H. VON BOEHMER: Thymus Development 19
R. CEREDIG: Major Histocompatibility-Restricted
Cytolytic T-Lymphocyte Precursors from the
Thymus of In Vivo Primed Mice: Increased
Frequency and Resistance to Anti-Lyt-2 Antibody
Inhibition. With 1 Figure . . . . . . . . . 27
J.J.T. OWEN, E.J. JENKINSON, and R. KINGSTON:
Thymic Stem Cells: Their Interaction with the
Thymic Stroma and Tolerance Induction . . 35
Part B: Murine T-Cell Receptor Genes
M. STEINMETZ and Z. DEMBIC: Organization,
Rearrangement, and Diversification of Mouse T-
Cell Receptor Genes. With 1 Figure ..... 45
L. ADoRINI, G. PALMIERI, A. SETIE, E. ApPELLA, and
G. DORIA: Expression of T-Cell Receptor by a
Mouse Monoclonal Antigen-Specific Suppressor T-
Cell Line . . . . . . . . . . . . . . . . . . 53
H.U. WELTzmN and K. EICHMANN: Somatic
Variation of Antigen-Recognition Specificity in H-
2b_ TNP-Specific Cytotoxic T-Cell Clones .... 63
J.T. EpPLEN, S. ALI, A. RlNALDY, and M.M. SIMON:
The Change of Specificity, Karyotype, and
Antigen-Receptor Gene Expression is Correlated in
Cytotoxic T-Cell Lines . . . . . . . . . . . . 69
VIII Table of Contents
Part C: Phenotype and Functional Potential of T-Cell
Clones
H. VON BOEHMER: Introductory Remarks . . . . . 77
C.G. BROOKS: A Study of the Functional Potential of
Mouse T-Cell Clones . . . . . . . . . . . . . 79
J.P. TITE, B. JONES, M.E. KATZ, and C.A. JANEWAY:
Generation, Propagation, and Variation in Cloned,
Antigen-Specific, la-Restricted Cytolytic T-Cell
Lines . . . . . . . . . . . . . . . . . . . . 93
B. FLEISCHER and H. WAGNER: Significance ofT4 or
T8 Phenotype of Human Cytotoxic T-Lymphocyte
Clones. With 1 Figure ........... 101
K. SHORTMAN and A. WILSON: Natural and
Unnatural Killing by Cytolytic T Lymphocytes.
With 2 Figures ............ ... 111
G. PAWELEC, F.-W. BUSCH, E.M. SCHNEIDER, A.
REHBEIN, I. BALKO, and P. WERNET: Acquisition of
Suppressive and Natural Killer-Like Activities
Associated with Loss of Alloreactivity in Human
"Helper" T-Lymphocyte Clones. With 3 Figures 121
J. HEUER, E. KOLSCH, and K. REsKE: Expression and
Function of Class II I-Ak Antigens on an Antigen
Specific T-Suppressor Cell Clone. With 2 Figures 131
Part D: Signal Requirements for T-Cell Activation
H. WAGNER: Introductory Remarks ..... . 141
H. WAGNER and C. HARDT: Heterogeneity of the
Signal Requirements During the Primary
Activation of Resting Lyt-2 + Cytotoxic T
Lymphocyte (CTL) Precursors into Clonally
Developing CTL. With 2 Figures . . . . . 143
A.C. OCHOA, G. GROMO, S.-L. WEE, and F.H. BACH:
Regulation of Lytic Function by Recombinant IL2
and Antigen. With 4 Figures ....... 155
T. HONIG: The Target Structure for Ti1: A Cell
Interaction Molecule Involved in T-Cell
Activation? With 3 Figures . . . . . . .. . 165
M.M. SIMON, S. LANDOLFO, T. DIAMANTSTEIN, and
U. HOCHGESCHWENDER: Antigen- and Lectin-
Sensitized Murine Cytolytic T Lymphocyte-
Table of Contents IX
Precursors Require Both Interleukin 2 and
Endogenously Produced Immune (y) Interferon for
Their Growth and Differentiation. With 3 Figures 173
H.R. MACDoNALD and F. ERARD: Activation
Requirements for Resting T Lymphocytes .. 187
Part E: Self-Nooself Discrimination in the T-Cell
Compartment
M. FELDMANN: Introductory Remarks .. 197
G.J.V. NOSSAL, B.L. PIKE, M.F. GOOD, J.F.A.P.
MILLER, and J.R. GAMBLE: Functional Clonal
Deletion and Suppression as Complementary
Mechanisms in T Lymphocyte Tolerance 199
M. FELDMANN, J.R. LAMB, and M. LONDEI: Human
T Cell Clones, Tolerance, and the Analysis of
Autoimmunity. With 1 Figure . . . . . . . . . 207
M.H. CLAESSON and C. ROPKE: Antiself Suppressive
(Veto) Activity of Responder Cells in Mixed
Lymphocyte Cultures. With 6 Figures .... 213
H.-D. HAUBECK, O. KLOKE, and E. KOLSCH:
Analysis of T Suppressor Cell Mediated Tumor
Escape Mechanisms. With 2 Figures .... . 225
M.K. HOFFMANN, M. CHUN, J.A. HIRST, and U.
HAMMERLING: The T-Cell Receptor Recognizes
Nominal and Self Antigen Independently. A
Theoretical Alternative to the Modified Self
Concept. With 3 Figures ........... 231
Part F: T-Cell-Mediated Autoreactivity
R.G. MILLER: Introductory Remarks . . . 241
J. REIMANN, K. HEEG, D. KABELITZ, H. WAGNER,
and R.G. MILLER: T-Cell Reactivity to
Polymorphic MHC Determinants. 1. MHC-Guided
T -Cell Reactivity .............. 243
K. HEEG, D. KABELITZ, H. WAGNER, and J.
REIMANN: T-Cell Reactivity to Polymorphic MHC
Determinants. II. Self-Reactive and Self-Restricted
T Cells. With 6 Figures . . . . . . . . . . . . 259
D. KABELITZ, K. HEEG, H. WAGNER, and J.
REIMANN: T-Cell Reactivity to Polymorphic MHC
X Table of Contents
Determinants. III. Alloreactive and Allorestricted
T Cells. With 9 Figures .... : ....... 275
P. BENVENISTE and R.G. MILLER: Appearance of
New Specificities in Lectin-Induced T-Cell Clones
Obtained from Limiting Dilution T-Cell Cultures.
With 2 Figures ............... 291
M.H. CLAESSON and C. ROPKE: Syngeneic
Cytotoxicity and Veto Activity in Thymic
Lymphoid Colonies and Their Expanded Progeny.
With 4 Figures ............... 301
T. SAITO and K. RA.mwSKY: Functional Analysis of
a Self-I-A Reactive T-Cell Clone Which
Preferentially Stimulates Activated B Cells 311
Indexed in Current Contents
List of Contributors
MORINI, L., ENEA-Euratom Immunogenetics Group,
Laboratory of Pathology, CRE Casaccia, CP 2400,
1-00100 Rome AD
ALI, S., Max-Planck-Institut fiir Immunobiologie, Stiibe
weg 51, D-7800 Freiburg
ANDREWS, P., Walter and Eliza Hall Institute of Medical
Research, Post Office, Royal Melbourne Hospital, Victo
ria 3050, Australia
MELLA, E., Laboratory of Cell Biology, NCI, NIH, Beth
esda, MD 20205, USA
BACH, F.H., Immunobiology Research Center, Depart
ments of Laboratory Medicine, Pathology, and Surgery,
University of Minnesota, MN 55455, USA
BALKO, I., Immunology Laboratory, Medizinische Klinik,
D-7400 Tiibingen
BENVENISTE, P., Ontario Cancer Institute and Department
of Immunology, University of Toronto, 500 Sherbourne
St., Toronto, Ontario M4X 1K9, Canada
BOEHMER, H. VON, Basel Institute for Immunology, Grenz
acher Str. 487, CH-4005 Basel
BoYD, R., Department of Pathology and Immunology,
Monash University Medical School, Melbourne, Austra
lia
BROOKS, C.G., Basic Immunology, Fred Hutchinson Can
cer Research Center, 1124 Columbia Street, Seattle,
WA 98104, USA
BUSCH, F.-W., Immunology Laboratory, Medizinische
Klinik, D-7400 Tiibingen
CEREDIG, R., Ludwig Institute for Cancer Research, Lau
sanne Branch, CH-1066 Epalinges