LFA-1 on CD4+ T cells is required for optimal antigen-dependent activation in vivo

S Kandula, C Abraham - The Journal of Immunology, 2004 - journals.aai.org
S Kandula, C Abraham
The Journal of Immunology, 2004journals.aai.org
The leukocyte-specific integrin, LFA-1, plays a critical role in trafficking of T cells to both
lymphoid and nonlymphoid tissues. However, the role of LFA-1 in T cell activation in vivo
has been less well understood. Although there have been reports describing LFA-1-deficient
T cell response defects in vivo, due to impaired migration to lymphoid structures and to sites
of effector function in the absence of LFA-1, it has been difficult to assess whether T cells
also have a specific activation defect in vivo. We examined the role of LFA-1 in CD4+ T cell …
Abstract
The leukocyte-specific integrin, LFA-1, plays a critical role in trafficking of T cells to both lymphoid and nonlymphoid tissues. However, the role of LFA-1 in T cell activation in vivo has been less well understood. Although there have been reports describing LFA-1-deficient T cell response defects in vivo, due to impaired migration to lymphoid structures and to sites of effector function in the absence of LFA-1, it has been difficult to assess whether T cells also have a specific activation defect in vivo. We examined the role of LFA-1 in CD4+ T cell activation in vivo by using a system that allows for segregation of the migration and activation defects through the adoptive transfer of LFA-1-deficient (CD18−/−) CD4+ T cells from DO11. 10 Ag-specific TCR transgenic mice into wild-type BALB/c mice. We find that in addition to its role in trafficking to peripheral lymph nodes, LFA-1 is required for optimal CD4+ T cell priming in vivo upon sc immunization. CD18−/− DO11. 10 CD4+ T cells primed in the lymph nodes demonstrate defects in IL-2 and IFN-γ production. In addition, recipient mice adoptively transferred with CD18−/− DO11. 10 CD4+ T cells demonstrate a defect in OVA-specific IgG2a production after sc immunization. The defect in priming of CD18−/− CD4+ T cells persists even in the presence of proliferating CD18+/− CD4+ T cells and in lymphoid structures to which there is no migration defect. Taken together, these results demonstrate that LFA-1 is required for optimal CD4+ T cell priming in vivo.
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