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Biomedical subjects

S Sriram

Publications and source records attributed to S Sriram.

At least 91 records · Page 5Linked to original sources
PubMed1988

Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma.

Collagen-induced arthritis (CIA) is an experimental model in which a specific immune response to type II collagen (CII) is associated with the development of inflammatory arthritis. In this study, we evaluated the effects of early and delayed treatments with anti-Ia mAb and IFN-gamma on murine CIA. Administration of anti-Ia mAb at the time of immunization with CII decreased the incidence and delayed the onset of arthritis, whereas anti-Ia treatments begun 2 wk after immunization had no effect upon either arthritis incidence or onset. Neither treatment protocol resulted in a significant decrease in antibody titer or proliferative response to CII. Because IFN-gamma increases Ia expression in a variety of cells, we determined its effect on arthritis incidence and onset. When IFN-gamma treatments were begun at the time of immunization the incidence of arthritis was increased and arthritis onset was more rapid. Treatment with IFN-gamma did not result in an increase in anti-CII antibody levels. These results support the importance of Ia expression in the induction of murine collagen-induced arthritis, and suggest that suppression with anti-Ia antibodies and augmentation with IFN-gamma are not the result of changes in the humoral response to CII, but may be due to local effects within the target organ.

Adjuvants, Immunologic↗
PubMed1988

In vivo immunomodulation by monoclonal anti-CD4 antibody. II. Effect on T cell response to myelin basic protein and experimental allergic encephalomyelitis.

In vivo administration of anti-CD4 mAb (GK1.5) has been shown to be effective in preventing acute and relapsing experimental allergic encephalomyelitis (EAE). In the present report we have studied the depletion of CD4+ cells by a single dose of GK1.5 on the immune response to myelin basic protein and in the development of EAE. Our studies show that depletion of CD4 cells in mice that had received encephalitogenic CD4+ T cells altered the kinetics of acute and relapsing EAE, but did not prevent disease altogether. The in vitro T cell proliferative response to myelin basic protein in lymph node cells was maintained in the presence of significant depletion of CD4+ cells. These studies indicate that the population of Ag-reactive cells to be large and relatively refractory to antibody therapy. The implication of these results to therapy of human autoimmune disease is discussed.

Adjuvants, Immunologic↗
PubMed1988

Successful therapy of Theiler's virus-induced demyelination (DA strain) with monoclonal anti-Lyt-2 antibody.

The effects of therapy with mAb to T cell subsets were studied in mice with Theiler's murine encephalomyelitis virus-induced demyelination. mAb GK1.5 (directed at class II-restricted T cells) and mAb 2.43 (directed at class I-restricted T cells) depleted the appropriate subset of T cells in lymph nodes, spleens, and peripheral blood for 6 to 8 wk after a single i.p. injection of 1 mg of purified mAb. Early treatment with mAb GK1.5 (days -1, 0, and +1 relative to virus injection) resulted in death, encephalitis, and increased demyelination in the majority of animals tested. Treatment with mAb 2.43 resulted in less meningeal inflammation and fewer demyelinating lesions in the spinal cord, irrespective of whether the mAb was given early or after demyelinating disease was established (days 15, 16, and 17). Beneficial response to mAb therapy did not correlate with titers of virus isolated from the central nervous system or serum. These results indicate an important role of class II-restricted T cells during early disease in preventing overwhelming encephalitis; class I-restricted T cells may be critical during demyelination.

Animals↗
PubMed1988

Clonal diversity of myelin basic protein-specific T lymphocytes.

A panel of myelin basic protein (MBP)-specific, class II major histocompatibility complex (As)-restricted T-cell clones were established from SJL/J mice. Three clonotypes, based on their responses to guinea pig MBP and its peptide fragments, were observed. Clonotype I cells, represented by clones HS.6, HS.D2, HS.8, HS.E10, and HS.C1, were reactive to the encephalitogenic C-terminal fragment of MBP, amino acid residues 89-169. Clonotype II, represented by clone HS.E3, was reactive to fragments containing residues 43-88, and clones HS.D12 and HS.C7, representing clonotype III cells, responded to the whole molecule only. Three clones from clonotype I were capable of transferring both clinical and histological signs of experimental allergic encephalomyelitis (EAE) into naive mice. Southern blot analysis of T-cell receptor beta-chain genes using J beta 1- and J beta 2-specific probes showed that the rearrangement pattern was unique in each of the clones. These results suggest that the development of EAE may represent an autoaggressive polyclonal T-cell response.

Animals↗
PubMed1988

In vivo depletion of Lyt-2 cells fails to alter acute and relapsing EAE.

The cellular mechanisms of recovery and relapses in experimental allergic encephalomyelitis (EAE) are not known. In order to determine the role of the suppressor/cytotoxic T lymphocytes (Lyt-2+) in EAE we studied the effect of in vivo depletion of this subset using monoclonal antibodies. Intraperitoneal injection of 1 mg of monoclonal antibody 2.43 resulted in rapid depletion of Lyt-2+ cells from lymph node, spleen and blood. Depletion of this subset had no effect on the kinetics of development, severity, and duration of acute EAE. Furthermore, following recovery from acute EAE administration of 2.43 did not result in development of relapses that were different in onset or severity from control animals. These results suggest that T cells of the Lyt-2 phenotype do not play a significant role in the immunoregulation of EAE.

Acute Disease↗
PubMed1988

In vivo modulation of murine collagen induced arthritis.

The effects of in vivo modulation of murine collagen induced arthritis with monoclonal anti-CD4 antibodies, monoclonal anti-Ia antibodies, and gamma interferon are reviewed. We detail the mechanism of action of monoclonal anti-CD4 antibody on humoral and cell mediated immune responses and discuss the implications for designing therapeutic strategies. To further explore the induction of collagen induced arthritis, a syngeneic cell transfer system using collagen primed T lymphocytes is described. This cell transfer system provides an opportunity to study the role of CD4 positive T lymphocytes in arthritis induction during a short, defined time period.

Animals↗
PubMed1987

Haplotype-specific suppression of experimental allergic encephalomyelitis with anti-IA antibodies.

Treatment with monoclonal antibodies directed against the IA antigens of the MHC is known to alter the course and prevent a number of experimental autoimmune diseases. To determine whether the treatment in vivo with anti-IA antibodies is haplotype-specific, we studied the development of EAE in F1 (SJL/J X BALB/c) mice following anti-IA antibody therapy. We report that treatment of animals with monoclonal antibody directed against the high responder allele product, I-As, was successful in preventing disease when therapy was begun either at the time of immunization with antigen, or following passive transfer of MBP-sensitized T cells. Therapy with antibody directed to the low responder allele product (I-Ad), while effective when used at the time of immunization with antigen, was ineffective following passive transfer of MBP-sensitized lymphocytes.

Alleles↗
PubMed1987

In vivo immunomodulation by monoclonal anti-L3T4. 1. Effects on humoral and cell-mediated immune response.

The in vivo administration of monoclonal anti-L3T4 antibody has been shown to be an effective preventative and, in some cases, therapeutic treatment for several murine models of autoimmune disease. This report deals with the effect of such treatments on humoral and cell-mediated responses to T-dependent antigens. Both the primary and secondary IgG responses to tetanus toxoid were inhibited when anti-L3T4 was administered prior to immunization, but it was ineffective in modulating an ongoing IgG response. Cell-mediated immunity, as detected by in vitro antigen-specific proliferative responses, was inhibited only if anti-L3T4 was given prior to immunization. It was not effective if treatment was delayed until 48 hr prior to lymph node harvest even though greater than 90% of L3T4+ lymph node cells were depleted by this treatment. The refractory behavior of the lymph node cells to anti-L3T4 treatment was not exhibited by antigen-primed cells obtained from peripheral blood or spleen. The importance of these findings with regard to antibody therapy for chronic autoimmune disease is discussed.

Animals↗
PubMed1986

Treatment of established chronic relapsing experimental allergic encephalomyelitis with anti-L3T4 antibodies.

CR-EAE is an autoimmune T cell-mediated disease that can be induced in mice either by the injection of MSCH and CFA or by passive transfer of MBP-sensitized T cells. To evaluate the clinical relevance of anti-L3T4 antibodies in this relapsing, remitting disease, we studied the therapeutic benefits of such treatment on CR-EAE in animals when treatment was begun after the onset of initial paralytic signs. Animals treated biweekly with anti-L3T4 antibody had fewer relapses than control animals, and the histopathology of the brain and spinal cord showed fewer and less extensive lesions. Serial analysis of lymph node cell populations and antibody levels showed that animals treated with anti-L3T4 antibody had a depletion of the helper/inducer T cell population and did not develop a humoral response to the administered rat antibody. This study raises the possibility of treatment with antibodies against T cell subsets in established disease wherein this subset is known to play a crucial role.

Animals↗
PubMed1985

Prevention of type II collagen-induced arthritis by in vivo treatment with anti-L3T4.

The effect of in vivo administration of monoclonal anti-L3T4 antibody on the development of murine collagen-induced arthritis (CIA) was assessed. Treatment with anti-L3T4 resulted in a greater than 90% depletion of L3T4+ T cells in lymph nodes and spleen, an effect that appears entirely reversed 30 d after treatment. Administration of anti-L3T4 before immunization with type II collagen resulted in a significant decrease in arthritis incidence and delayed onset of the disease while treatment begun after a strong anticollagen IgG humoral response was underway was not effective in altering disease expression. These results suggest a prominent role for L3T4+ T cells in the pathogenesis of CIA.

Animals↗
PubMed1985

Reversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker.

Administration of a monoclonal antibody (GK1.5) that recognizes the L3T4 marker present on helper T cells prevented the development of experimental allergic encephalomyelitis (EAE) in mice. Furthermore, treatment with GK1.5 reversed EAE when the antibody was given to paralyzed animals. In vivo injection of GK1.5 selectively reduced the number of L3T4+ cells in the spleen and the lymph nodes. These results suggest that manipulation of the human equivalent of the murine L3T4+ T-cell subset with monoclonal antibodies may provide effective therapy for certain autoimmune diseases.

Animals↗
PubMed1985

HLA-DR antigens in multiple sclerosis: two-dimensional gel electrophoresis.

Fifty to eighty percent of white patients with clinically definite MS express the DR2 antigen. In patients and normal controls who possess the DR2 antigens, analysis of the polymorphic light chain by two-dimensional polyacrylamide gel electrophoresis revealed no structural differences.

Antibodies, Monoclonal↗