High-frequency alloreactive T cells augment effector function of low-frequency CD8+ T-cell responses under CD28/CD154 blockade.
BACKGROUND
Blockade of costimulatory molecules is a potent method of inducing long-term graft survival. We have previously addressed the issue of donor-reactive T-cell precursor frequency on relative costimulation dependence and found that the presence of a high precursor frequency of donor-reactive CD8 T cells resulted in costimulation blockade-resistant graft rejection, whereas the presence of a low-frequency donor-reactive population did not. To address the mechanisms by which high-frequency T cells obviated the requirement for costimulation, we asked whether a low-frequency population responding concomitantly with a high-frequency response also demonstrated costimulation independence.


METHODS
A model system was established in which B6 mice containing a low frequency of anti-membrane bound chicken ovalbumin (mOVA) responders and a high frequency of anti-BALB/c responders received a skin graft from B6.mOVAxBALB/c F1 donors in the presence or absence of cytotoxic T-lymphocyte antigen-4 Ig/anti-CD154 costimulatory blockade.


RESULTS
The results revealed that in the presence of costimulation blockade, high-frequency anti-BALB/c T cells augmented the effector activity of low-frequency anti-mOVA T cells, but it did not enhance the accumulation of anti-mOVA T cells capable of mediating graft rejection.


CONCLUSIONS
These results demonstrate that both antigen-specific and antigen-independent factors contribute to the relative costimulation independence of high-frequency T-cell responses.
Floyd
Tamara L
TL
Orr
Steven B
SB
Coley
Shana M
SM
Hanna
Samantha S
SS
Wagener
Maylene E
ME
Kirk
Allan D
AD
Larsen
Christian P
CP
Ford
Mandy L
ML
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000494:pharmacology; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015533:Transcriptional Activation; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D010047:Ovalbumin
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