RESUMO
Coronin 1, a member of the evolutionary conserved WD repeat protein family of coronin proteins is expressed in all leukocytes, but a role for coronin 1 in natural killer (NK) cell homeostasis and function remains unclear. Here, we have analyzed the number and functionality of NK cells in the presence and absence of coronin 1. In coronin 1-deficient mice, absolute NK cell numbers and phenotype were comparable to wild type mice in blood, spleen and liver. Following in vitro stimulation of the activating NK cell receptors NK1.1, NKp46, Ly49D and NKG2D, coronin 1-deficient NK cells were functional with respect to interferon-γ production, degranulation and intracellular Ca2+ mobilization. Also, both wild type as well as coronin 1-deficient NK cells showed comparable cytotoxic activity. Furthermore, activation and functionality of NK cells following Vesicular Stomatitis Virus (VSV) infection was similar between wild type and coronin 1-deficient mice. Taken together these data suggest that coronin 1 is dispensable for mouse NK cell homeostasis and function.
Assuntos
Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Animais , Biomarcadores , Cálcio/metabolismo , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Imunofenotipagem , Células Matadoras Naturais/ultraestrutura , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Camundongos , Camundongos Knockout , Fenótipo , Receptores de Células Matadoras Naturais/agonistas , Receptores de Células Matadoras Naturais/metabolismo , Baço/citologia , Baço/imunologia , Baço/metabolismoRESUMO
Coronin 1 is a member of the evolutionary conserved WD repeat protein family and is highly expressed in hematopoietic cells. Coronin 1 is essential for Ca(2+) mobilization upon T cell receptor (TCR) stimulation providing a pro-survival signal for naïve peripheral T cells. Both in mouse and in human, coronin 1 deficiency is associated with severe T cell lymphopenia. In this work, we have analyzed antiviral T cell-mediated immunity in the presence and absence of coronin 1 in vivo after infection with lymphocytic choriomenigitis virus (LCMV) and vesicular stomatitis virus (VSV) in mice. Despite low peripheral T cell numbers we found that LCMV-specific CD8(+) T cell responses were normal in the absence of coronin 1 and kinetics of LCMV-clearance were similar compared to wild type mice. In contrast, CD4(+) T cell responses were profoundly decreased after LCMV- and VSV-infection. We propose that coronin 1 plays a differential role in CD8(+) versus CD4(+) T cell responses and activation.