We have previously reported that stomatin-like protein 2 (SLP-2) regulates human T cell activation through the antigen receptor. In human lymphoid tissues, SLP-2 is widely expressed in the thymus, lymph nodes and tonsils, and its expression is further up-regulated in response to lymphocyte activation. In T cells, SLP-2 is found in two pools: the most abundant is associated with mitochondria while a smaller pool is associated with the plasma membrane. To further investigate the role of SLP-2, we generated T cell-specific SLP-2 deficient mice. These mice had normal numbers of thymocytes and mature T cells. However, SLP-2 deficient T cells showed significantly less T cell activation in response to T cell stimulation in vivo and in vitro. Although SLP-2 deficient T cells did not show significant alterations in mitochondrial biogenesis, they had decreased levels of the NDUSF3, NDUFB8 and NDUFA9 subunits of complex I of the respiratory chain, suggesting a possible role for SLP-2 in regulating the stability of proteins involved in mitochondrial electron transport. SLP-2 deficient T cells also had less cardiolipin within detergent-insoluble microdomains, which may be required for proper respiratory chain assembly and function. Based on these results, we conclude that SLP-2 contributes to T cell activation, in part by regulating stability of complex I of the respiratory chain and sustaining the metabolic requirements for T cell activation.
- Copyright © 2011 by The American Association of Immunologists, Inc.