Homing and homeostasis of T lymphocytes in CD18 deficient mice
LicenseStandard (Fassung vom 01.10.2008)
Expressed on leukocytes, beta2 integrins (CD11/CD18) are involved in leukocyte function and trafficking. Using a CD18-deficient (CD18-/-) mouse model, the role of beta2 integrins for lymphocyte differentiation and recirculation was herein investigated. CD18-/- mice revealed a defect in distribution of naïve lymphocytes, which were reduced in numbers in axillary and inguinal lymph nodes (LN). In contrast, cervical LN (cLN) were signi¬ficantly enlarged and harbored elevated numbers of unconventional T cell receptor (TCR) alpha/beta or TCR gamma/delta double negative (DN) T cells. As demonstrated by adoptive transfer experiments, a selective homing of CD18-/- lymphocyte to pLN of wild type recipients was not the reason for this increase in cellularity. But unconventional DN T cells were found to be increased in cLNs due to a massive local expansion demonstrated by in vivo incorporation of thymidine analogue BrdU. In accordance, CD18-/- DN T cells showed an activated phenotype and recirculated through non-lymphoid organs resembling anti¬gen-experienced T and NKT cells. CD18-/- TCR alpha/beta DN T cells readily pro¬liferated upon IL-2, IL-7 and IL-15, known to regulate homeostasis or antigen-induced expansion of NKT and TCR gamma/delta T cells. In accordance with the assumption that CD18-/- TCR alpha/beta DN T cells are expanding effector cells, they also lacked suppressive function on proliferating WT T cell in vitro. Interestingly, CD18-/- TCR alpha/beta T cells revealed general characteristics of NKT cells but lacking re¬activity for CD1d/alpha-galactosylceramide showed that they were not type I NKT cells. Nevertheless, the possi¬bility that CD18-/- TCR alpha/beta DN T cells are a different subset of NKT cells cannot be fully excluded, currently. However, lack of IL-4 and IFN-gamma cytokine secretion after stimulation showed that CD18-/- TCR alpha/beta DN T cells may have different functional properties to NKT and TCR gamma/delta T cells in innate im¬munity. Collectively, DN T cells accumulated either due to antigen-dependent and/or homeostatic expansion in the periphery, likely driven by a cytokine imbalance in CD18-/- mice. The presented data indicates that CD18-/- TCR alpha/beta DN T cells, like NKT and TCR gamma/delta T cells, may be a unique subset of unconventional T cells at the interface to innate immunity accumulating compensatory to the impaired function of adaptive immunity in CD18-/- mice.
Subject HeadingsT-Lymphozyt [GND]
Animal models in research [MeSH]
Immunodeficiency Diseases [MeSH]
Mice. Immunology [MeSH]