Floyd, T. L., Orr, S. B., Coley, S. m., Hanna, S. S., Wagener, M. E., Kirk, A. D., Larsen, C. P. and Ford, M. L. (2010) High-frequency alloreactive T cells augment effector function of low-frequency CD8+ T-cell responses under CD28/CD154 blockade. Transplantation, 89(10), pp. 1208-1217. (doi: 10.1097/TP.0b013e3181df53dc) (PMID:20407401) (PMCID:PMC2935314)
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Abstract
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.mOVA×BALB/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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by NIH K22 AI079409 (M.L.F.) and NIH R37 AI40519 (C.P.L.). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Coley, Dr Shana |
| Authors: | Floyd, T. L., Orr, S. B., Coley, S. m., Hanna, S. S., Wagener, M. E., Kirk, A. D., Larsen, C. P., and Ford, M. L. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Transplantation |
| Publisher: | Lippincott, Williams and Wilkins for the Transplantation Society |
| ISSN: | 0041-1337 |
| ISSN (Online): | 1534-6080 |
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