Interleukin-2 Signaling and the Maintenance of Self-Tolerance

Author(s):  
B.H. Nelson
Keyword(s):  
1996 ◽  
Vol 81 (3) ◽  
pp. 282-286 ◽  
Author(s):  
Gabriele Klebb ◽  
Ingo B. Autenrieth ◽  
Hildegard Haber ◽  
Esther Gillert ◽  
Benjamin Sadlack ◽  
...  
Keyword(s):  

1995 ◽  
Vol 148 (1) ◽  
pp. 35-44 ◽  
Author(s):  
IVAN HORAK ◽  
Jurgen Lohler ◽  
AVERIL MA ◽  
KENDALL A. SMITH

1996 ◽  
Vol 184 (2) ◽  
pp. 387-396 ◽  
Author(s):  
M Asano ◽  
M Toda ◽  
N Sakaguchi ◽  
S Sakaguchi

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.


2005 ◽  
Vol 173 (4S) ◽  
pp. 214-214
Author(s):  
Shuji Terao ◽  
Toshiro Shirakawa ◽  
Kazumasa Goda ◽  
Sadao Kamidono ◽  
Akinobu Gotoh

1999 ◽  
Vol 56 (6) ◽  
pp. 330-333
Author(s):  
Dummer ◽  
Nestle ◽  
Hofbauer ◽  
Burg

Das metastasierende Melanom (MM) gehört zu den schwierig behandelbaren Malignomen, wobei Allgemeinzustand und Motivation des Patienten neben Zahl und Lokalisation der Metastasen das therapeutische Vorgehen bestimmen. Solitäre Metastasen in Lunge, ZNS, Weichteilen und Lymphknoten sollten primär chirurgisch entfernt werden. Multiple Metastasen, insbesondere abdominal, werden nur in Ausnahmefällen chirurgisch angegangen. Hier ist vielmehr ein systemische Chemoimmuntherapie angebracht. Aussichtsreiche Behandlungskonzepte beinhalten Interleukin-2, Interferon, und verschiedenen Zytostatika wie DTIC, Temozolamid, Vindesine oder Cisplatin. Bei ZNS- und Skelettfiliae ist die Radiotherapie einzusetzen. Durch diese Chemoimmuntherapien hat sich die Prognose des metastasierenden Melanoms bezüglich des Überlebens verbessert. Langfristig wird aber nur eine Kombination von zeitraubenden Multicenterstudien und experimentellen Ansätzen in der Lage sein, uns langsam an eine kurative Therapie heranzuführen.


2005 ◽  
Vol 75 (5) ◽  
pp. 357-368 ◽  
Author(s):  
Foote ◽  
Nonnecke† ◽  
Waters ◽  
Palmer ◽  
Beitz ◽  
...  

Effects of increased protein and energy provided by an intensified milk replacer on the antigen-specific, cell-mediated immune response of the neonatal calf were examined. Calves were fed a standard (0.45 kg/day of a 20% crude protein, 20% fat milk replacer; n = 11) or intensified (1.14 kg/day of a 28% crude protein, 20% fat milk replacer; n = 11) diet from 0 to 6 weeks of age. All calves were vaccinated with Mycobacterium bovis bacillus Calmette-Guerin (BCG) at 1 week of age. The daily weight gain of intensified-diet calves (0.62 kg/day) was greater than the weight gain of standard-diet calves (0.29 kg/day). Liver, kidney, heart, thymus, and subcervical lymph nodes from intensified-diet calves were heavier than the same organs from standard-diet calves. Flow cytometric analysis of peripheral blood mononuclear cell (PBMC) populations indicated that CD4+ cells, gamma delta TCR+ cells, and monocyte percentages, although unaffected by diet during the first 5 weeks of the study, were higher in intensified-diet calves at week 6. The decline in gamma deltad TCR+ cell percentages and increase in B cell percentages with increasing age seen in all calves are characteristic of the maturing immune system of the calf. CD8+ T cell or B cell percentages were not affected by diet. In intensified-diet calves, percentages of CD4+ expressing interleukin-2 receptor increased and percentages of gamma delta TCR+ cells expressing interleukin-2 receptor decreased with time. The same populations in standard-diet calves did not change with time. Percentages of CD4+ and CD8+ T cells, and B cells expressing MHC class II antigen, were unaffected by diet or age. Although mitogen-induced interferon (IFN)-gamma and nitric oxide (NO) secretion increased with age for all calves, PBMC from intensified-diet calves produced less IFN-gamma and more NO than did cells from standard-diet calves at week 6 of the study. Antigen-induced secretion of IFN-gamma and NO also increased with age but was unaffected by diet. Antigen-elicited delayed-type hypersensitivity was unaffected by diet, suggesting increased dietary protein and energy did not alter adaptive immunity in vivo. Overall, these results suggest that feeding calves a commercially available, intensified milk replacer affects minimally the composition and functional capacities of PBMC populations. Additional research is necessary to determine whether these subtle effects influence the calf’s susceptibility to infectious disease.


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