Subset-specific and temporal control of effector and memory CD4+ T cell survival.

Following their proliferative expansion and differentiation into effector cells like Th1, Tfh, and T central memory precursors (Tcmp), most effector CD4+ T cells die, while some survive and become memory cells. Here, we explored how Bcl-2 family members controlled the survival of CD4+ T cells during distinct phases of mouse acute LCMV infection. During expansion, we found that Th1 cells dominated the response, downregulated expression of Bcl-2, and did not require Bcl-2 for survival.

Bcl-2 Is Necessary to Counteract Bim and Promote Survival of TCRαβCD8αα Intraepithelial Lymphocyte Precursors in the Thymus.

The precursors of TCRαβCD8αα intraepithelial lymphocytes (IEL) arise in the thymus through a complex process of agonist selection. We and others have shown that the proapoptotic protein, Bim, is critical to limit the number of thymic IEL precursors (IELp), as loss of Bim at the CD4CD8 double-positive stage of development drastically increases IELp. The factors determining this cell death versus survival decision remain largely unknown.

T-cell receptor signal strength and epigenetic control of Bim predict memory CD8 T-cell fate.

Most effector CD8 T cells die, while some persist and become either "effector" (T) or "central" (T) memory T cells. Paradoxically, effector CD8 T cells with greater memory potential have higher levels of the pro-apoptotic molecule Bim. Here, we report, using a novel Bim-mCherry knock-in mouse, that cells with high levels of Bim preferentially develop into T cells.

Dying to protect: cell death and the control of T-cell homeostasis.

T cells play a critical role in immune responses as they specifically recognize peptide/MHC complexes with their T-cell receptors and initiate adaptive immune responses. While T cells are critical for performing appropriate effector functions and maintaining immune memory, they also can cause autoimmunity or neoplasia if misdirected or dysregulated. Thus, T cells must be tightly regulated from their development onward.

dysregulation of CD1d-restricted type ii natural killer T cells leads to spontaneous development of colitis in mice.

Background & Aims: CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis.

Isoforms of the nonclassical class I MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide.

Although the human nonclassical class Ib major histocompatibility complex (Mhc) locus, HLA-G, is known to act as an immune suppressor in immune-privileged sites, little is currently known regarding participation of the rodent class Ib Mhc in similar pathways. Here, we investigated the expression properties of the mouse nonclassical Mhc H2-Q5(k) gene, previously detected in tumors and tissues associated with pregnancy. We find that H2-Q5(k) is alternatively spliced into multiple novel isoforms in a wide panel of C3H tissues.