A role for B and T lymphocyte attenuator in regulating T cell responses during Tuberculosis (P3088)

Abstract B and T lymphocyte attenuator (BTLA) (CD272) is a coinhibitory receptor expressed by most leukocytes, with the highest expression levels observed on T and B cells, and is involved in the maintenance of peripheral tolerance by dampening the activation of lymphocytes. We wanted to determine if BTLA signaling played a role in T cell meditated regulation during tuberculosis infection. The expression of BTLA was examined on activated (CD44hiCD62Llo) CD4+ T cells in lungs, spleen and lymph nodes in mice during pulmonary Mycobacterium tuberculosis infection. The expression of BTLA on activated CD4+ T cells increased at day 10 post-infection in lungs, when compared to naïve mice, but then declined at day 21 post-infection. In the spleen and lymph nodes while the number of cells expressing BTLA increased, the expression of BTLA on these cells did not increase. Although the number of CD4+BTLA+ T cells in the lungs had increased at day 21, these cells expressed lower levels of BTLA than at day 10, suggesting that BTLA expression was down-regulated during this time. We also found an increase in the percentage of activated and effector memory T cells in the organs when BTLA was blocked using an anti-BTLA antibody during early stage of tuberculosis infection. Further, increased bacterial load was observed in the lungs of mice treated with anti-BTLA antibody indicating that BTLA regulates T cell-driven exacerbation of infection during the early stages of tuberculosis.