Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy

The expression of cutaneous leukocyte antigen (CLA) and CC-chemokine receptor 4 (CCR4; associated with skin-homing) as well as the expression of integrin α4β7 and CCR9 (associated with gut-homing) was analyzed on CD4+ memory T cells in CSF from individuals with non-inflammatory neurological diseases using flow cytometry. CSF contained similar proportions of CD4+ memory T cells expressing CLA, CCR4, integrin α4β7 and CCR9 as paired blood samples.The results extend our previous findings that antigen-experienced CD4+ memory T cells traffic through the CSF in proportion to their abundance in the peripheral circulation. Furthermore, the ready access of skin- and gut-homing CD4+ memory T cells to the CNS compartment via CSF has implications for the mechanisms of action of immunotherapeutic strategies, such as oral tolerance or therapeutic immunization, where immunogens are administered using an oral or subcutaneous route.The differentiation of na？ve T cells into an activated memory phenotype is characterized by an extensive change in the expression of trafficking determinants, resulting in the acquisition of homing receptors that enable the cells to migrate from the circulation into peripheral tissues. This change in T cell homing potential is affected by the microenvironment where initial antigen recognition occurred, as memory T cells preferentially return to regions of the body similar to those where the initial antigen was encountered [1]. For instance, studies in mice have demonstrated that CD4+ T cells activated in cutaneous lymph nodes upregulate trafficking determinants specific for the skin, such as P-selectin ligand, while T cells responding to antigen in intestinal lymph nodes express high levels the gut-associated adhesion molecule integrin α4β7 and acquire responsiveness to the intestinal CC-chemokine ligand CCL25 [2]. The specific profile of adhesion molecules and chemoattractant receptors expressed by individual T cells allows the cells to interact with the