title: Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells.
abstract: After scald burn-injury, the intestinal immune system responds to maintain immune balance. In this regard CD4+T cells in Gut-Associated Lymphoid Tissues (GALT), like mesenteric lymph nodes (MLN) and Peyer's patches (PP) respond to avoid immune suppression following major injury such as burn. Therefore, we hypothesized that the gut CD4+T cells become dysfunctional and turn the immune homeostasis towards depression of CD4+ T cell-mediated adaptive immune responses. In the current study we show down regulation of mucosal CD4+ T cell proliferation, IL-2 production and cell surface marker expression of mucosal CD4+ T cells moving towards suppressive-type. Acute burn-injury lead to up-regulation of regulatory marker (CD25+), down regulation of adhesion (CD62L, CD11a) and homing receptor (CD49d) expression, and up-regulation of negative co-stimulatory (CTLA-4) molecule. Moreover, CD4+CD25+ T cells of intestinal origin showed resistance to spontaneous as well as induced apoptosis that may contribute to suppression of effector CD4+ T cells. Furthermore, gut CD4+CD25+ T cells obtained from burn-injured animals were able to down-regulate naïve CD4+ T cell proliferation following adoptive transfer of burn-injured CD4+CD25+ T cells into sham control animals, without any significant effect on cell surface activation markers. Together, these data demonstrate that the intestinal CD4+ T cells evolve a strategy to promote suppressive CD4+ T cell effector responses, as evidenced by enhanced CD4+CD25+ T cells, up-regulated CTLA-4 expression, reduced IL-2 production, tendency towards diminished apoptosis of suppressive CD4+ T cells, and thus lose their natural ability to regulate immune homeostasis following acute burn-injury and prevent immune paralysis.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chicago State University, Chicago, IL 60628, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Fazal
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Chicago State University, Chicago, IL 60628, USA.
authors.forename: Alla
authors.initials: A
authors.lastname: Shelip
authors.affiliation: Department of Clinical laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Alhusain J
authors.initials: AJ
authors.lastname: Alzahrani
keywords: Apoptosis; CD4+CD25+ T cells; Immune homeostasis; Immune suppression; Mesentric lymph nodes; Peyer's patches