Phenotyping analysis of peripheral blood leukocytes in patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is a central nervous disease thought to be elicited by an autoimmune process. Many studies in recent years have concentrated on finding the alterations in the peripheral blood immune profile in MS patients that would reflect disease activity. In the present study, we investigated surface antigen expression on lymphocytes and granulocytes from MS patients and control subjects. We have studied 29 patients suffering from relapsing-remitting or relapsing-progressive forms of MS. The disease was diagnosed in all patients at least 12 months before inclusion into the study. All patients had no attack at the study entry date or within a previous month. The control group included 29 age-matched subjects. Phenotyping of peripheral blood leukocytes was carried out with different fluorescence-conjugated murine monoclonal antibodies. The analysis was performed with three-color flow cytometry. The following antigens were determined [cluster of definition (CD)]: leukocyte common antigen (LCA) (B220, T 200, Ly-5), CD45; LPS-R (lipopolysaccharide receptor), CD14; found on all T cells, CD3; LFA-2 (lymphocyte function associated antigen, T 11), CD2; coreceptor for MHC class II molecules, found on helper T cells, CD4; coreceptor for MHC class I molecules, found on suppressor/cytotoxic T cells, CD8; B4, found on all human B cells, CD19; NCAM (neural cell adhesion molecule), CD56; integrin beta2 subunit, associated with CD11a (CD11a/CD18, LFA-1, alphaLbeta2) and CD11b (CD11b/CD18, Mac-1,CR3, alphaMbeta2), CD18; alphaL, alpha subunit of integrin LFA-1 (alphaLbeta2, CD11a/CD18), CD11a; alphaM, alpha subunit of integrin Mac-1 (CR3, alphaMbeta2, CD11b/CD18), CD11b; ICAM-1 (intercellular adhesion molecule), CD54; H-CAM, Hermes antigen, Pgp-1, CD44; AIM (activation inducer molecule), early activation antigen, CD69; T-cell receptor gammadelta, TCR gammadelta. In the MS group, we have found a significant increased expression of CD54 and CD44 antigens on lymphocytes, and higher percentage CD54(+) and CD11a+CD54(+) lymphocytes out of all lymphocytes compared with the control group. We have also found a significant increased expression of CD11a, CD18 and CD54 antigens on granulocytes, and higher percentage CD11b+CD18(+) granulocytes out of all granulocytes in MS patients compared with control. Higher levels of expression of the adhesion molecules may reflect the activation state of leukocytes in MS patients.

B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity

“…Our current findings are confirmed by reports of an increased number of B cells during MS relapses [61], and significantly increased levels of the B-cell survival promoter APRIL in MS patients [69]. Recently, short-lived plasma blasts were identified as the main effector B cell population involved in active inflammation in MS patients [70].…”

“…However, it is now emerging that other cell types, i.e. B cells, and also other factors are important [59-61]. Unlike activated T cells, B cells do not appear to cross the intact BBB, whereas the occurrence of BBB damage in MS does permit the entry of B cells and antibodies into the CNS [62] presumably augmenting the characteristic intrathecal antibody synthesis found in a majority of MS patients.…”

γδ T Cells Participating in Nervous Systems: A Story of Jekyll and Hyde

“…As a potentially disabling disease of the CNS, multiple sclerosis (MS) is caused by the immune system attacking on protective myelin sheaths that cover neurons, eventually disabling the communication between brain and the rest of the body (45). Though many comparisons among patients with primary progressive MS, patients with relapsing-remitting MS (RRMS), healthy controls and patients with other neurological diseases have been done and the differences of the frequency of gd T cells in the peripheral blood in patients with MS remains contradictory (54)(55)(56)(57)(58).While the percentage of Vd2 T cells decreased and the percentage of Vd1 T cells increased in peripheral blood of MS patients (58, 59), gd T cells in MS patients expressed higher level of C-X-C Motif Chemokine Receptor 3 (CXCR3) that was related to the migration of T cells to MS plaques (60). As one of the two ligands of CXCR3, IFN-g-induced protein 10 (IP-10) was elevated in both primary progressive MS and RRMS (61).…”

Role of Complement in Immune Regulation and Its Exploitation by Virus

“…CR3 is expressed on approximately 10-15% of resting CD3 ϩ T cells (136,181), the majority of which are CD8 ϩ T cells (181). Expression of CR3 on both CD8 ϩ and CD4 ϩ T cells increases after activation (181).…”