SPINAL-FLUID LYMPHOCYTES FROM A SUBGROUP OF MULTIPLE-SCLEROSIS PATIENTS RESPOND TO MYCOBACTERIAL ANTIGENS

Immune responses to heat shock or stress proteins are observed in seve ral chronic autoimmune diseases. Such proteins are major antigens of m any bacteria, especially mycobacteria. To determine whether immune res ponses to stress proteins occur in chronic inflammatory diseases of th e central nervous system such as multiple sclerosis (MS) we measured p roliferative 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 re call antigen. Significantly increased spinal fluid lymphocyte response s to mycobacterial sonicate, relative to responses from paired periphe ral blood lymphocytes, were present in 14 of 20 specimens from patient s with MS (p < 0.025) and 2 of 9 specimens from patients with other ne urological diseases. Spinal fluid lymphocytes also responded to tetanu s toxoid, but differences between blood and spinal fluid were not stat istically significant. Lymphocytes from 1 patient with MS responded on ly to M. leprae. There were no proliferative responses to the M. tuber culosis acetone extract. When patients with MS were classified accordi ng to duration of disease (< 2- or > 2-yr duration) 9 of 10 patients w ith recent onset had cerebrospinal fluid cells that responded to M. tu berculosis compared with 5 of 10 with longer duration symptoms (p < 0. 012). Our data suggest a selective recruitment and/or expansion of myc obacterial reactive cells to the central nervous system of a subpopula tion of patients with MS. Immune responses to antigens present in myco bacteria, possibly stress proteins, may be important in perpetuating a nd amplifying chronic inflammatory diseases of the central nervous sys tem such as MS.