Deficiency of CD11b or CD11d Results in Reduced Staphylococcal Enterotoxin-Induced T Cell Response and T Cell Phenotypic Changes

Abstract

The β2 integrin CD11a is involved in T cell-APC interactions, but the roles of CD11b, CD11c, and CD11d in such interactions have not been examined. To evaluate the roles of each CD11/CD18 integrin in T cell-APC interactions, we tested the ability of splenocytes of CD11-knockout (KO) mice to respond to staphylococcal enterotoxins (SEs), a commonly used superantigen. The defect in T cell proliferation with SEA was more severe in splenocytes from mice deficient in CD18, CD11b, or CD11d than in CD11a-deficient splenocytes, with a normal response in CD11c-deficient splenocytes. Mixing experiments showed that the defect of both CD11b-KO and CD11d-KO splenocytes was, unexpectedly, in T cells rather than in APC. Cytometric analysis failed to detect CD11b or CD11d on resting or activated T cells or on thymocytes of wild-type adult mice, nor did Abs directed to these integrins block responses in culture, suggesting that T cells educated in CD11b-KO or CD11d-KO mice were phenotypically altered. Consistent with this hypothesis, T cells from CD11b-KO and CD11d-KO splenocytes exhibited reduced intensity of CD3 and CD28 expression and decreased ratios of CD4/CD8 cells, and CD4+ T cells were reduced among CD11b-KO and CD11d-KO thymocytes. CD11b and CD11d were coexpressed on a subset of early wild-type fetal thymocytes. We postulate that transient thymocyte expression of both CD11b and CD11d is nonredundantly required for normal thymocyte and T cell development, leading to phenotypic changes in T cells that result in the reduced response to SE stimulation.

Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins

“…15 A recent study has also shown that CD11b may also govern T-cell development and function, in that the loss of CD11b decreased CD3 and CD28 expression and CD4/CD8 ratios. 60 Early reports dismissed a role for T cells in DSS colitis; however, recent reports suggest that this cell population may participate in a regulatory manner through influencing recruitment of specific leukocyte populations (ie monocytes vs granulocytes) or by providing growth factors necessary for epithelial cell survival and regeneration during DSS colitis. 26,28 Therefore, it is possible that CD11b deficiency may alter T-cell regulatory functions during DSS colitis.…”

Critical Requirement of CD11b (Mac-1) on T Cells and Accessory Cells for Development of Experimental Autoimmune Encephalomyelitis

“…This observation might indicate differences in functional activity of T regulatory cells between MAC-1-deficient and wild-type mice. At this time, it is unknown whether the pattern of cytokine production by Mac-1-deficient T cells in EAE is due to altered congenital T cell development (18).…”

“…This seems unlikely because T cells from Mac-1-deficent mice do respond, although less efficiently than wild-type T cells, to several staphylococcal superantigens (18) and to MOG peptide in in vitro restimulation assays (Fig. 5A).…”

A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice

“…As both LFA-1 and CD11b bind to ICAM-1 [22,24] and CD11b/ICAM-1 interactions promote the tissue adhesion of different cell populations [65][66][67][68], we also analyzed the expression of CD11b on iNKT cells. In contrast to conventional T cells [69], peripheral iNKT cells were CD11b + already under steady-state conditions. CD11b-expression was significantly increased on iNKT cells from slp-76 ace/ace mice with the majority of CD11b + iNKT cells accumulating in the peripheral lymph nodes (Fig.…”