Thymic selection of cytotoxic T cells independent of CD8 alpha-Lck association

Science ◽  
1993 ◽  
Vol 261 (5128) ◽  
pp. 1581-1584 ◽  
Author(s):  
I. Chan ◽  
A Limmer ◽  
M. Louie ◽  
E. Bullock ◽  
W. Fung-Leung ◽  
...  
1988 ◽  
Vol 168 (3) ◽  
pp. 1187-1192 ◽  
Author(s):  
R M Zinkernagel ◽  
E Rüedi ◽  
A Althage ◽  
H Hengartner ◽  
G Reimann

Mice with congenital severe combined immunodeficiency disease (SCID) failed to mount either a T cell-independent IgM or T cell-dependent IgG anti-vesicular stomatitis virus (VSV) Indiana (IND) response. They did not generate cytotoxic T cells against lymphocytic choriomeningitis virus (LCMV) or vaccinia virus, but exhibited NK cell-like activities. When SCID mice were given bone marrow from syngeneic BALB/c (H-2d) nu/nu mice, all immune responses were expressed at control levels. If SCID mice were reconstituted with allogeneic H-2b C57BL/6 nu/nu bone marrow, the following primary anti-viral immune responses were measured. T-independent IgM anti-VSV-IND were normal, but T-dependent IgG anti-VSV-IND responses were absent. Cytotoxic T cell responses to LCMV and vaccinia virus were within normal ranges, were donor cell mediated, and were specific exclusively for the recipient SCID H-2d type. Since antigen presentation by spleen cells was functional in these chimaeras, the presented results indicate that (a) thymic selection of T cell restriction is strict; and (b) the type of T help necessary for B cells depends upon H-2-restricted contact between T and B cells, whereas, such contact-dependent help is not mandatory for the induction of virus-specific cytotoxic T cells.


1978 ◽  
Vol 148 (3) ◽  
pp. 805-810 ◽  
Author(s):  
RM Zinkernagel ◽  
A Althage ◽  
S Cooper ◽  
G Callahan ◽  
J Klein

The H-2 haplotype of the chimeric host determines the responder phenotype of maturing T cells. Spleen cells of chimeric mice formed when (K(k) nonresponder to D(b) × K(b) responder to D(b) plus vaccinia)F(1) bone marrow cells were used to reconstitute K(b)D(b) (C57BL/6 D(b) responder) irradiated recipients generated high levels of D(b) plus vaccinia virus-specific cytotoxic T cells. The same stem cells used to reconstitute K(k)D(b) (B10.A (2R) D(b) nonresponder) irradiated recipients resulted in spleen cells that responded well to K plus vaccinia, but responsiveness to D(b) was low. A generally low response to D(k) plus vaccinia, which seems to be regulated by D(k), was confirmed in chimeras. Thus, K(d)D(d) (D(d) plus vaccinia responder) stem cells differentiating in a K(d)D(k) chimeric host failed to generate a measurable response to D(k) plus vaccinia. In contrast, stem cells from K(d)D(k) (D(k) plus vaccinia low responders) differentiating in a K(d)D(d) (K(d) and D(d) high responders to vaccinia) host do generate responsiveness to D(d) plus vaccinia. These results indicate that in chimeras, the Ir phenotype is independent of the donor T cell's Ir genotype, and that thymic selection of a T cell's restriction specificity for a particular H-2 allele of the chimeric host also defines that T cell's Ir phenotype.


2019 ◽  
Vol 10 ◽  
Author(s):  
Yang Li ◽  
Nato Teteloshvili ◽  
Shulian Tan ◽  
Samhita Rao ◽  
Arnold Han ◽  
...  

2010 ◽  
Vol 71 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Masao Hashimoto ◽  
Mitsutaka Kitano ◽  
Kazutaka Honda ◽  
Hirokazu Koizumi ◽  
Sachi Dohki ◽  
...  

1984 ◽  
Vol 160 (2) ◽  
pp. 552-563 ◽  
Author(s):  
A R Townsend ◽  
J J Skehel

Using genetically typed recombinant influenza A viruses that differ only in their genes for nucleoprotein, we have demonstrated that repeated stimulation in vitro of C57BL/6 spleen cells primed in vivo with E61-13-H17 (H3N2) virus results in the selection of a population of cytotoxic T lymphocytes (CTL) whose recognition of infected target cells maps to the gene for nucleoprotein of the 1968 virus. Influenza A viruses isolated between 1934 and 1979 fall into two groups defined by their ability to sensitize target cells for lysis by these CTL: 1934-1943 form one group (A/PR/8/34 related) and 1946-1979 form the second group (A/HK/8/68 related). These findings complement and extend our previous results with an isolated CTL clone with specificity for the 1934 nucleoprotein (27, 28). It is also shown that the same spleen cells derived from mice primed with E61-13-H17 virus in vivo, but maintained in identical conditions by stimulation with X31 virus (which differs from the former only in the origin of its gene for NP) in vitro, results in the selection of CTL that cross-react on target cells infected with A/PR/8/1934 (H1N1) or A/Aichi/1968 (H3N2). These results show that the influenza A virus gene for NP can play a role in selecting CTL with different specificities and implicate the NP molecule as a candidate for a target structure recognized by both subtype-directed and cross-reactive influenza A-specific cytotoxic T cells.


2002 ◽  
Vol 168 (2) ◽  
pp. 613-620 ◽  
Author(s):  
Rafal Pacholczyk ◽  
Piotr Kraj ◽  
Leszek Ignatowicz

2009 ◽  
Vol 106 (12) ◽  
pp. 4810-4815 ◽  
Author(s):  
M. A. Wallet ◽  
R. R. Flores ◽  
Y. Wang ◽  
Z. Yi ◽  
C. J. Kroger ◽  
...  

1989 ◽  
Vol 170 (1) ◽  
pp. 177-190 ◽  
Author(s):  
F I Preffer ◽  
C W Kim ◽  
K H Fischer ◽  
E M Sabga ◽  
R L Kradin ◽  
...  

CD7+CD3- cells purified (greater than 99.99%) by FACS from the peripheral blood of healthy adults include precursors for mature T cells that have the capacity to differentiate into TCR-1+ or TCR-2+ CD3+ cells. Extrathymic differentiation was demonstrable from all eight healthy donors in the presence of a high concentration of IL-2, mitogenic levels of PHA, and irradiated blood mononuclear feeder cells, after a lag of approximately 40 d in vitro. The extrathymic T (ET) cells were predominantly TCR-1+, although TCR-2+ cells were also derived. ET TCR-1+ cells were CD4-CD8-, CD4-CD8DIM+, and CD4+CD8-, and were distinguished from natural T TCR-2+ cells by a variety of cell surface markers. The ET cells had phenotypes generally displayed by normal mature T cells, although the CD5DIM+ on ET cells was more typical of thymocytes. Acquisition of CD3 on purified CD7+CD3- cells was not due to antigenic modulation or growth of contaminants, and ET cells could be demonstrated at the clonal level. Studies in athymic mice and bone marrow recipients support the view that extrathymic maturation does occur in vivo. Whether the CD7+CD3- cell population was unexposed to the thymus, or exposed but not processed, is unknown. In any case, unusual or "forbidden" autoreactive specificities are predicted since ET cells differentiate without thymic selection of the TCR.


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