Relative increase of inflammatory CD4 + T cells in the cerebrospinal fluid of multiple sclerosis patients and control individuals

SUMMARY Of three patients with multiple sclerosis (MS) and two non‐MS individuals a large number of CD4 + T cell clones was obtained from the cerebrospinal fluid and peripheral blood by direct limiting dilution. The CD4 + T cell clones from cerebrospinal fluid and peripheral blood lymphocytes were compared for their cytotoxic activity and lymphokine production. Cytotoxic capacity of cloned T cells was analysed with the use of anti‐CD3 antibodies and target cells bearing Fc receptors for murine IgG. Recently, we demonstrated the existence of two different subsets of human CD4 + T cell clones by phenotypic and functional criteria. One type of CD4 + T cell with anti‐CD3 mediated cytotoxic activity, in analogy with murine studies, is the inflammatory or T H1 subtype, the main producer of interleukin (IL‐2), interferon‐gamma (IFN‐γ) and tumour necrosis factor (TNF)‐α, ‐β, whereas the other type of CD4 + T cell clone lacked anti‐CD3 mediated cytotoxicity and produced minimal amounts of IL‐2 concomitant with reduced levels of IFN‐γ and TNF‐α, ‐β. The present study demonstrates that among three MS patients, relatively more inflammatory CD4 + T cell clones with cytotoxic activity and IFN‐γ and TNF‐α, ‐β production were derived from the cerebrospinal fluid as compared with peripheral blood lymphocytes. Also among control individuals more inflammatory CD4 + T cell clones could be obtained from the cerebrospinal fluid as from the peripheral blood. The enrichment of inflammatory CD4 + T cells, therefore, appears to be physiological rather than associated with the disease.