B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo: Increased Interleukin 12 Production by DCs from B Cell–Deficient Mice Results in T Helper Cell Type 1 Deviation

Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (μMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and μMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-γ, interleukin (IL)-2, and IL-4, whereas those from μMT mice produced IFN-γ and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-γ, and IL-2, whereas administration of DCs from μMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from μMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response

C-Terminal Mutants of Apolipoprotein L-I Efficiently Kill Both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense

Apolipoprotein L-I (apoL1) is a human-specific serum protein that kills Trypanosoma brucei through ionic pore formation in endosomal membranes of the parasite. The T. brucei subspecies rhodesiense and gambiense resist this lytic activity and can infect humans, causing sleeping sickness. In the case of T. b. rhodesiense, resistance to lysis involves interaction of the Serum Resistance-Associated (SRA) protein with the C-terminal helix of apoL1. We undertook a mutational and deletional analysis of the C-terminal helix of apoL1 to investigate the linkage between interaction with SRA and lytic potential for different T. brucei subspecies. We confirm that the C-terminal helix is the SRA-interacting domain. Although in E. coli this domain was dispensable for ionic pore-forming activity, its interaction with SRA resulted in inhibition of this activity. Different mutations affecting the C-terminal helix reduced the interaction of apoL1 with SRA. However, mutants in the L370-L392 leucine zipper also lost in vitro trypanolytic activity. Truncating and/or mutating the C-terminal sequence of human apoL1 like that of apoL1-like sequences of Papio anubis resulted in both loss of interaction with SRA and acquired ability to efficiently kill human serum-resistant T. b. rhodesiense parasites, in vitro as well as in transgenic mice. These findings demonstrate that SRA interaction with the C-terminal helix of apoL1 inhibits its pore-forming activity and determines resistance of T. b. rhodesiense to human serum. In addition, they provide a possible explanation for the ability of Papio serum to kill T. b. rhodesiense, and offer a perspective to generate transgenic cattle resistant to both T. b. brucei and T. b. rhodesiense

IL-4 induces CD22 expression to restrain the effector program of virtual memory T cells.

peer reviewedParasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8+ T cells (TVM cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4-dependent TVM cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8+ T cells to identify pathways that control IL-4-dependent TVM cell responses. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a selective surface marker of IL-4-induced TVM cells. CD22+ TVM cells were enriched for interferon-γ and granzyme A and retained a diverse TCR repertoire while enriched in self-reactive CDR3 sequences. CD22 intrinsically regulated the IL-4-induced CD8+ T cell effector program, resulting in reduced responsiveness of CD22+ TVM cells and regulatory functions to infection and inflammation. Thus, helminth-induced IL-4 drives the expansion and activation of TVM cells that is counterinhibited by CD22

Un nouveau mode d'inactivation des lymphocytes T helper: Découplage du récepteur antigénique du système de transmission des signaux d'activation

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Un nouveau mode d'inactivation des lymphocytes T helper: Découplage du récepteur antigénique du système de transmission des signaux d'activation

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

AMPK in Lymphocyte Metabolism and Function.

Adenosine monophosphate-activated protein kinase (AMPK) is a serine/threonine kinase that is crucial for cellular energy metabolism homeostasis. AMPK monitors cellular energy status in response to nutritional variations and, once activated by low energy status, switches on ATP-producing catabolic pathways and switches off ATP-consuming anabolic pathways to restore cellular energy homeostasis. When T lymphocytes encounter foreign antigens, they initiate a program of differentiation leading to the rapid generation of effector and memory cells that clear the pathogen and prevent future infection, respectively. Differentiation of naïve T cells in effector or long term memory cells is tightly associated with changes in their energy metabolic activity and recent data have revealed that fine-tuning of metabolism could modulate T cell functions. Here, we will review recent data about the regulation of T cell metabolism by AMPK and discuss its influence on T cell function.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Physiology and physiopathology of the immune system: initiation and termination of immune responses

info:eu-repo/semantics/publishe

L'apomorphine: facile et efficace

info:eu-repo/semantics/publishe