Cerebral cortex and brainstem involvement in marinesco‐sjögren syndrome

10) and control subjects (n = 9); however, the small sample size may not allow comparison to our previously reported studies in the peripheral blood in which the abnormality was not seen in all patients. Regarding the percentage of CD4 + CD45RA + T cells in the blood reported by Salonen and co-workers [3}, they examined 8 patients with relapsing-remitting disease. The decrease we observed was seen in chronic progressive, not relapsing-remitting, patients [2}. As to the “reproducibility” of the decrease in CD4+CD45RA+ cells in subjects with MS, four laboratories (including ours) have found decreases of CD4 + CD45RA + T cells in patients wilth MS ([3-71; J. Wolinsky, personal communication, 1989). We know of no report in which these changes have not been observed in progressive MS. Two laboratories have reported decreases in CD4+CD45RA+ T cells in other neurological diseases (OND) 13, 71 whereas three laboratories have not [2, 4, 5}. Why this discrepancy exists is not known, although it should be pointed out that the O N D control subjects represent a heterogeneous group of patients, and other factors such as age, medications, and the general medical condition of patients must be taken into account. Elias postulates that the decreased expression of the CD4+CD45RA+ is part of a general response to tissue (myelin) damage rather than an underlying basis for an autoimmune response. Theoretically all immunological observations made in MS may be secondary phenomena since patients are studied after the disease has expressed itself. Nonetheless, a number of studies in other autoimmune diseases argue against this. The decrease of CD4 + CD45RA + T cells in blood and a low autologous mixed lymphocyte response (AMLR) are found in a number of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis (reviewed in [S}) , where there is no myelin damage. In addition, in MS there is a close correlation between the number of circulating CD4 + CD45RA +T cells and other immunological abnormalities such as loss of nonspecific suppression and decreases in the AMLR [9}. The decrease in nonspecific suppression that has been identified in MS for a number of years and which is linked to the CD4 + CD45RA + subset does not explain the specific injury to CNS white matter that occurs in MS. As mentioned, similar changes are seen in other autoimmune diseases, and in our view these changes represent a dysregulated immune system that allows organ-specific autoimmune processes to be expressed depending on the genetic makeup of the host and environmental factors. It has also been postulated that the CD4 + CD45RA + T cell represents so-called “naive” T cells while a reciprocal CD4 + CDW29 + population of T cells are memory T cells [lo}, thus suggesting that the decrease in CD4 + CD45 RA + T cells is simply secondary to the heightened state of activation of the immune system. Recent data show that this is not necessarily the case. For example, we have recently observed a subpopulation of long-term T-cell clones that express CD45RA with activation but not at rest, indicating that the CD4 + CD45RA + T cell may not represent only naive cells fll}. In addition, preliminary work from our laboratory suggests that cells taken from the blood of MS patients and control subjects that are activated in vivo are CD4 + CD45RA + (J. LaSalle, D.A. Hafler, unpublished data). More work is needed to define the relationship between cell activation and CD4 + CD45RA+ expression in vivo. Ultimately, the degree to which an immunological abnormality in MS is primarily involved in disease expression can only be answered by specific manipulation of the abnormality with a subsequent ameliorative effect on the disease course.