Burn injury induces a change in T cell homeostasis affecting preferentially CD4+ T cells

Abstract

Burn injuries are known to be associated with altered immune functions, resulting in decreased resistance to subsequent infection. In the present study, we determined the in vivo changes in T cell homeostasis following burn injury. Two groups of mice were used: a sham-burn group receiving buprenorphine as an analgesic and a burn group receiving buprenorphine and subjected to burn injury on 20% of the total body surface area. Results showed an important decrease in splenocytes following burn injury. This decrease persisted for 5 days and was followed, at day 10, by a 63% increase in number of cells. In vivo cell proliferation, as determined by the incorporation of 5-bromo-2'-dexoxyuridine, showed a significant increase of cycling splenocytes between days 2 and 10 after burn injury. The percentage of CD4+ and CD8+ T cells in the spleen was altered for 10 days after thermal injury. Analysis of naive (CD62Lhigh CD44low) and effector/memory (CD62Llow CD44high) T cells showed a percent decrease, independent of the expression of CD4 or CD8 molecules. However, early activation markers, such as CD69+, were expressed only on CD4+ T cells after a number of days following injury. Even with an activated phenotype, 10 days post-burn injury, CD4+ naive T cells significantly increased spontaneous apoptosis, detected by using a fluorescent DNA-binding agent 7-amino-actinomycin D. CD8+ T lymphocytes did not express early activation markers and were more resistant to apoptosis. Using purified T cells, we have shown unresponsiveness at day 10. Overall, these results demonstrate that mechanisms of T cell homeostasis were perturbed following burn injury. However, after 10 days, this perturbation persisted only in CD4+ T cells.