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.

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

“…These cells were identified as CD4 ϩ T cells with both naive (CD62 ϩ ) and memory (CD44 ϩ ) showing the same pattern when exposed to CORT. This result confirms our previous report, which showed a specific effect on CD4 ϩ T cells at day 10 postburn (34).…”

“…T cell dysfunction occurring past day 10 postinjury has been linked to increased morbidity and mortality of burn-injured patients (2). Also, previous reports from our group and others' have noted hyperresponsive T lymphocytes on day 7 and later postburn injury (23,27,34). Furthermore, we have shown in a time course study that T cell functions were modified at day 10 postburn injury.…”

“…GC responsiveness in T cells that either were selected or survived during these crucial first 5 days postburn has never been addressed. Since T cell dysfunction has been demonstrated at day 10 postburn injury by our group and others (23,27,34) and was linked to their hyperactive status, we hypothesize that this situation could be the result of a loss of sensitivity to GC.…”

“…Furthermore, we have shown in a time course study that T cell functions were modified at day 10 postburn injury. Splenic T lymphocytes demonstrated an activated phenotype, spontaneous apoptosis, and an overall unresponsiveness to antigen-induced stimulation (34).…”

Indicators of apoptosis lymphocytes of peripheral blood in experimental thermal injury in the application of transdermal films with erythropoietin

“…Некоторые патогенетиче-ские механизмы, лежащие в ее основе, приводят к развитию осложнений как системных (вторич-ный иммунодифицит, сепсис, септический шок, полиорганная недостаточность), так и местных (инфицирование раневой поверхности, образова-ние патологических рубцов, нарушение двига-тельных функций). Известно, что при ТТ наблю-дается лимфоцитопения, это может являться важным фактором патогенеза иммунной дис-функции [1, 2]. В связи с этим, терапия ТТ должна включать как системное, так и местное воздействие.…”