Immune responses to heat shock or stress proteins are observed in several chronic autoimmune diseases. Such proteins are major antigens of many bacteria, especially mycobacteria. To determine whether immune responses to stress proteins occur in chronic inflammatory diseases of the central nervous system such as multiple sclerosis (MS) we measured proliferative responses of lymphocytes from spinal fluids and bloods of patients with MS and other neurological diseases to a sonicate of M. tuberculosis, an acetone extract of M. tuberculosis, a recombinant 65-kd heat shock protein of M. leprae, and tetanus toxoid as a control recall antigen. Significantly increased spinal fluid lymphocyte responses to mycobacterial sonicate, relative to responses from paired peripheral blood lymphocytes, were present in 14 of 20 specimens from patients with MS (p < 0.025) and 2 of 9 specimens from patients with other neurological diseases. Spinal fluid lymphocytes also responded to tetanus toxoid, but differences between blood and spinal fluid were not statistically significant. Lymphocytes from 1 patient with MS responded only to M. leprae. There were no proliferative responses to the M. tuberculosis acetone extract. When patients with MS were classified according to duration of disease (< 2- or > 2-yr duration) 9 of 10 patients with recent onset had cerebrospinal fluid cells that responded to M. tuberculosis compared with 5 of 10 with longer duration symptoms (p < 0.012). Our data suggest a selective recruitment and/or expansion of mycobacterial reactive cells to the central nervous system of a subpopulation of patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS)

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