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Acute lung injury (ALI) is a frequent pulmonary complication in critically ill patients. We characterized a murine model of LPS-induced ALI, focusing on Th cells. Following LPS administration, bronchoalveolar lavage lymphocytes, neutrophils, IL-6, TNF-alpha, and albumin were increased. Analysis of LPS-induced T cells revealed increased Th cell-associated cytokines (IL-17A, -17F, and -22), as well as increased expression of CD69 (a cell activation marker), Foxp3, and CTLA4 in CD4(+) T cells. Administration of anti-CTLA4 Ab decreased LPS-induced bronchoalveolar lavage albumin and IL-17A, while increasing CD4(+)Foxp3(+) cell number and Foxp3 expression in CD4(+)Foxp3(+) cells. These data suggest that pulmonary LPS administration promotes CD4(+) T cells and that T cell pathways involving CTLA4 contribute to ALI.

The generation of an allergic immune response requires at least two signals for complete activation of T cells. Costimulatory molecules are integral to the second signal. In this review, we analyze the costimulatory molecule signaling lymphocytic activation molecule (SLAM) and other recently described SLAM family members. We highlight recent findings that position SLAM as critical for allergic inflammation and its role in modulation of cytokine secretion. Furthermore, a possible role of SLAM as a link between the adaptive and innate immune response is also discussed. Understanding the role of costimulatory molecules, including SLAM and SLAM family members, may elucidate mechanisms involved in the allergic immune response, and suggest potential therapeutic opportunities.