DECREASED DEPENDENCE OF MYELIN BASIC PROTEIN-REACTIVE T-CELLS ON CD28-MEDIATED COSTIMULATION IN MULTIPLE-SCLEROSIS PATIENTS - A MARKER OF ACTIVATED MEMORY T-CELLS/

Although multiple sclerosis (MS) patients and healthy individuals have similar frequencies of myelin basic protein (MBP)-specific T cells, t he activation state of these cells has not been well characterized, Th erefore, we investigated the dependence of MBP-reactive T cells on CD2 8-mediated costimulation in MS patients, healthy controls, and stroke patients, MBP-reactive T cells from healthy controls and stroke patien ts failed to proliferate efficiently when costimulation was blocked us ing anti-CD28, consistent with a naive T cell response. In contrast, M BP-specific T cell proliferation was not inhibited, or was only partia lly inhibited when CD28-mediated costimulation was blocked in MS patie nts. Blockade of CD28 failed to inhibit tetanus toxoid-specific T cell proliferation in both the controls and MS patients, demonstrating tha t memory cells are not dependent on CD28-mediated costimulation, Limit ing dilution analysis indicated that the frequency of MBP-reactive T c ells was significantly decreased in healthy controls compared with MS patients when CD28-mediated costimulation was blocked, These data sugg est that MBP-reactive T cells are more likely to have been activated i n vivo and/or differentiated into memory T cells in MS patients compar ed with controls, indicating that these cells may be participating in the pathogenesis of MS.