Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis

نویسندگان

  • Sara Wojciechowski
  • Pulak Tripathi
  • Tristan Bourdeau
  • Luis Acero
  • H. Leighton Grimes
  • Jonathan D. Katz
  • Fred D. Finkelman
  • David A. Hildeman
چکیده

We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2(-/-) mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim(+/-)Bcl-2(-/-) mice, but were largely restored in Bim(-/-)Bcl-2(-/-) mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim(-/-), T cells. Further, T cells from Bim(+/-)Bcl-2(-/-) mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8(+) T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4(+) T cells did not. In contrast, Bim(+/-)Bcl-2(-/-) mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim(+/-)Bcl-2(-/-) mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways in human naive and IgM+ memory B cells through altering balances in Bcl-2 family proteins.

BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM(+) memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis ...

متن کامل

Distinct but complementary roles of Fas ligand and Bim in homeostatic T cell apoptosis.

The adaptive immune system, as mediated by T cells and B cells, plays an essential role in host defense. Throughout adult life the total number of T cells remains fairly constant, suggesting that their expansion and retraction is tightly regulated. However, in response to infection or immunization antigen-specific T cells must expand and develop various effector functions enabling them to rapid...

متن کامل

Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim.

As acute infections resolve, most effector CD8(+) T cells die, whereas some persist and become memory T cells. Recent work showed that subsets of effector CD8(+) T cells, identified by reciprocal expression of killer cell lectin-like receptor G1 (KLRG1) and CD127, have different lifespans. Similar to previous reports, we found that effector CD8(+) T cells reported to have a longer lifespan (i.e...

متن کامل

Role of Bim in regulating CD8+ T-cell responses during chronic viral infection.

Apoptosis is critical for the development and maintenance of the immune system. The proapoptotic Bcl-2 family member Bim is important for normal immune system homeostasis. Although previous experiments have shown that Bim is critical for the apoptosis of antigen-specific CD8(+) T cells during acute viral infection, the role of Bim during chronic viral infection is unclear. Using lymphocytic cho...

متن کامل

Disruption of T Cell Homeostasis in Mice Expressing a T Cell–Specific Dominant Negative Transforming Growth Factor β II Receptor

The immune system, despite its complexity, is maintained at a relative steady state. Mechanisms involved in maintaining lymphocyte homeostasis are poorly understood; however, recent availability of transgenic (Tg) and knockout mouse models with altered balance of lymphocyte cell populations suggest that cytokines play a major role in maintaining lymphocyte homeostasis. We show here that transfo...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 204  شماره 

صفحات  -

تاریخ انتشار 2007