TY - JOUR
T1 - Suppressor cell regulation of encephalitogenic T cell lines
T2 - Generation of suppressor macrophages with cyclosporin A and myelin basic protein
AU - Whitham, Ruth H.
AU - Vandenbark, Arthur A.
AU - Bourdette, Dennis N.
AU - Chou, Yuan K.
AU - Offner, Halina
N1 - Funding Information:
’ This work was supported by the Veterans Administration, the Medical Research Foundation of Oregon, and NIH Grants NS 2322 I and NS 23444. ‘Correspondence and reprint requests should be addressedt o Ruth Whitham M.D., Neurology Service 127, VA Medical Center, Portland, OR 97207. 3 Abbreviations used: APC, antigen presenting cells; BP, myelin basic protein; CFA, complete Freund’s adjuvant; Con A, concanavalin A; cpm, counts per minute; CR-EAE, chronic relapsing EAE; CsA, cyclosporin A; EAE, experimental allergic encephalomyelitis; IFA, incomplete Freund’s adjuvant; LNC, lymph node cells; MS, multiple sclerosis; PPD, purified protein derivative of mycobacterium.
PY - 1990/4/1
Y1 - 1990/4/1
N2 - Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) can be adoptively transferred using myelin basic protein (BP)-specific helper T cell lines, and suppressor cells may be important in recovery from EAE. In order to generate suppressor cells, spleen cells obtained from BP-complete Freund's adjuvant (CFA) inoculated SJL/J mice and from normal mice were cultured for 7 days with medium, with cyclosporin A (CsA), or with CsA and antigen (BP or purified protein derivative of mycobacterium (PPD)). Cultured spleen cells were assayed for suppressor activity in vitro by coculture with BP-specific and PPD-specific helper T cell lines derived from SJL/J mice. Immunized donor spleen cells cultured with cyclosporin A (CsA) and BP were potent inhibitors of T cell line proliferation, and suppressor activity was increased 17-fold compared with control splenocytes. The number of suppressor cells required to suppress PPD-specific line proliferation by 50% (I50) was significantly higher than the number required to suppress BP-specific line proliferation, suggesting an antigen-specific component to the suppression. The major effector cell required for suppression was a large granular Mac-1 + cell with the functional characteristics of a macrophage. Suppressor activity persisted after depletion of Thy 1.2+ cells, but suppression was no longer antigen-specific, suggesting that culture of spleen cells with CsA and BP may generate suppressor macrophages which are antigen-nonspecific and Thy 1.2+ suppressor cells which are antigen-specific. These suppressor cells may be important in the regulation of CR-EAE and the techniques described for their generation may prove useful for treatment and prevention of disease.
AB - Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) can be adoptively transferred using myelin basic protein (BP)-specific helper T cell lines, and suppressor cells may be important in recovery from EAE. In order to generate suppressor cells, spleen cells obtained from BP-complete Freund's adjuvant (CFA) inoculated SJL/J mice and from normal mice were cultured for 7 days with medium, with cyclosporin A (CsA), or with CsA and antigen (BP or purified protein derivative of mycobacterium (PPD)). Cultured spleen cells were assayed for suppressor activity in vitro by coculture with BP-specific and PPD-specific helper T cell lines derived from SJL/J mice. Immunized donor spleen cells cultured with cyclosporin A (CsA) and BP were potent inhibitors of T cell line proliferation, and suppressor activity was increased 17-fold compared with control splenocytes. The number of suppressor cells required to suppress PPD-specific line proliferation by 50% (I50) was significantly higher than the number required to suppress BP-specific line proliferation, suggesting an antigen-specific component to the suppression. The major effector cell required for suppression was a large granular Mac-1 + cell with the functional characteristics of a macrophage. Suppressor activity persisted after depletion of Thy 1.2+ cells, but suppression was no longer antigen-specific, suggesting that culture of spleen cells with CsA and BP may generate suppressor macrophages which are antigen-nonspecific and Thy 1.2+ suppressor cells which are antigen-specific. These suppressor cells may be important in the regulation of CR-EAE and the techniques described for their generation may prove useful for treatment and prevention of disease.
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U2 - 10.1016/0008-8749(90)90322-I
DO - 10.1016/0008-8749(90)90322-I
M3 - Article
C2 - 1690080
AN - SCOPUS:0025218040
SN - 0008-8749
VL - 126
SP - 290
EP - 303
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -