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Biomedical subjects

C Rohowsky-Kochan

Publications and source records attributed to C Rohowsky-Kochan.

33 records · Page 2Linked to original sources
PubMed1991

Serum soluble interleukin-2 receptor levels in chronic progressive, stable and steroid-treated multiple sclerosis.

Serum levels of the soluble interleukin-2 receptor (sIL-2R), an indicator of T cell activation, were significantly elevated in chronic progressive MS (CPMS) patients, clinically stable MS patients and in patients with other neurological diseases (OND) as compared to healthy controls. Levels of sIL-2R in steroid treated CPMS patients were markedly lower than in untreated CPMS patients and were comparable to healthy controls. Thus, systemic T cell activation occurs in MS during clinically stable and progressive disease stages and in other neurological disorders. The ability of oral corticosteroids to depress serum sIL-2R levels in vivo may be one mechanism by which they exert their therapeutic effect.

Adult↗
PubMed1991

Clinical correlation with serum-soluble interleukin-2 receptor levels in Guillain-Barré syndrome.

In patients with Guillain-Barré syndrome (GBS) soluble interleukin-2 receptor (sIL-2R) levels were elevated compared with those of patients with other neurologic diseases (OND), and of healthy controls. Smaller increases in sIL-2R levels occurred in OND patients compared to healthy subjects. Monitoring of GBS patients clearly demonstrated that decreases in sIL-2R levels correlated with clinical recovery. Thus, T-cell activation may be relevant in the pathogenesis of GBS.

Central Nervous System Diseases↗
PubMed1990

Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases.

Decreased numbers of CD4+CD45R+ suppressor-inducer T cells have been reported in patients with a variety of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis but not in patients with other neurological diseases. We now report our findings using murine monoclonal antibodies and two-color flow cytometric analysis on CD4+CD45R+ T cells in 22 patients with chronic progressive multiple sclerosis, 23 patients with other neurological diseases and 42 normal, healthy controls. Suppressor-inducer T cells were significantly reduced (p less than 0.001) in both patients with multiple sclerosis and other neurological diseases as compared to controls. Both patient populations had elevated helper T cell subset ratios. Thus, our data suggests that decreases in suppressor-inducer T cells may represent a common immunological defect among autoimmune and presumably non-autoimmune neurological disorders.

Adult↗
PubMed1989

MHC-restricted autoantigen-reactive T cell clones in multiple sclerosis.

Multiple sclerosis is a demyelinating disease of the central nervous system with genetic, viral and autoimmune characteristics. Myelin basic protein (MBP) is a suspected target autoantigen since it induces experimental autoimmune encephalomyelitis, an animal model closely resembling multiple sclerosis. The disease is mediated by Class II restricted, MBP-reactive T cells possessing the T helper/inducer phenotype. In the present study, we have isolated MBP-reactive T cell clones from the peripheral blood of a chronic progressive multiple sclerosis patient. The clones displayed blastogenic memory responses when rechallenged with the autoantigen and irradiated autologous lymphocytes. MBP recognition by the autoantigen-reactive T lymphocytes was restricted by major histocompatibility complex Class II antigens. Both CD4+8- and CD4-8+ MBP-reactive T cell clones were obtained.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros.

To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.

Adult↗
PubMed1986

Functional modifications of alloreactive T cell clones infected with HTLV-I.

Two alloreactive T cell clones with anti-HLA-DR1 specificity showed significant alterations of cognitive and functional characteristics after infection with human T cell leukemia virus (HTLV-I). Similar to HTLV-I-infected lines derived from immunologically uncommitted lymphocytes, the transformed clones displayed blastogenic mixed lymphocyte culture (MLC) responses to cells carrying any of the allelic variants of human HLA-D/DR antigens, including self. Although these two clones were originally able to provide allospecific help only to B cells expressing the DR1 antigen, after infection with HTLV-I they stimulated B cells of any HLA-D/DR phenotype to produce immunoglobulin in cultures. The helper inducer activity of the transformed clones remained susceptible to the effect of monoclonal antibody anti-LDA1 that inhibits the helper function of normal human T cells. One of these clones (207TK), which before infection specifically killed DR1-positive target cells, lost its killing ability. The other clone (19TK) although originally noncytotoxic, acquired natural killer-like function after transformation. Study of the rearrangement of the genes coding for the beta-chain of the T cell antigen receptor revealed no differences between the wild (noninfected) and mutant (infected) clones. There was, however, an increased level of this message, as well as of the message encoded by the beta-chain gene of HLA-DR in the mutant clones. Such changes may be related to transacting transcriptional effects induced by the human T cell lymphotropic virus HTLV-I.

Antibodies, Monoclonal↗
PubMed1986

Perturbation of the immune network in herpes gestationis.

We have studied the development of anti-idiotypic antibodies to HLA and of autoantibodies reacting with alloactivated T lymphoblasts in a woman with herpes gestationis (HG). This primigravida developed an elevated titer of anti-HLA antibodies, (Ab1), in association with a low titer and late appearance of anti-anti-HLA antibodies (Ab2). At delivery she developed only minimal levels of antibodies reacting with autologous T lymphoblasts (T1), sensitized against the immunizing HLA antigens of the child. Her serum reacted, however, with T lymphoblasts, primed in AMLC against autologous T blasts alloactivated in vitro against her husband (T2). Because healthy gravidae do not show such antibodies, it appears that they are peculiar to and may represent a perturbation of the idiotypic network in regard to the immune

Autoantibodies↗
PubMed1985

Idiotypic network regulations of immune responses to HLA.

The development of antiidiotypic autoimmunity with respect to HLA alloantigens provides an attractive explanation for the phenomenon of maternal tolerance to the fetus and for the tandem selection of two antagonistic traits, major histocompatibility complex polymorphism and alloreactivity. We have demonstrated that both T and B lymphocyte responses to allogeneic HLA antigens are subjected to feedback regulation by autologous antiidiotypic immunity. Idiotypic receptors for the alloantigen expressed by T lymphocytes induce antiidiotypic antibodies that are readily detectable in serum during pregnancy, and antiidiotypic T cells that can be revealed in the autologous mixed lymphocyte culture system. Such antiidiotypic T cells and antibodies inhibit specifically the alloimmune function of autologous T cell lines. Similarly, antiidiotypic antibodies (Ab2) to HLA antibody molecules (Ab1) block the binding of the latter to the immunizing HLA antigen. The prevalence of Ab2 over Ab1 during pregnancy may explain the maternal tolerance to the fetus.

Animals↗
PubMed1984

Modulation of T-cell antigen receptor on lymphocyte membrane.

A mouse monoclonal antibody, Mo. Ab. 108.45, detecting cell-surface determinants associated with the T-cell receptor for alloantigen was produced by immunizing mice with an alloreactive human T-cell clone and fusing the splenocytes with the NS1 plasmocytoma. This Mo. Ab. reacts with the immunizing T-cell clone but not with autologous or allogeneic lymphocytes, lymphoblasts or monocytes; stimulates the proliferation of the immunizing T cells in the absence of the alloantigen; inhibits the response to the specific stimulator; and precipitates a disulfied linked heterodimer composed of two distinct glycoproteins of molecular weights 40000 and 46000. The receptor molecule detected by Mo. Ab. 108.45 modulates on the surface of the cells, reaching the highest levels 5 days following exposure to the specific stimulator. The receptor-associated molecule detected by Mo. Ab. 108.45 was expressed by T-cell clones obtained independently in two different mixed lymphocyte cultures between the same responder and stimulator.

Antibodies, Monoclonal↗
PubMed1984

Enhancement of idiotype-anti-idiotype T cell interactions by monoclonal OKT11A antibody.

We have demonstrated that OKT11A, a mouse monoclonal antibody recognizing the E receptor on human T lymphocytes, strongly enhances the autologous mixed lymphocyte culture (AMLC) response induced by T lymphoblasts, while inhibiting the AMLC response induced by B lymphoblasts as well as the T cell response to alloantigens and soluble antigens. This antibody seems to enhance the idiotype-anti-idiotype interaction between resting and activated T lymphocytes.

Adult↗
PubMed1984

Functional characterization of human alloreactive T cell clones.

We have investigated the functional activity of alloreactive T cell clones, generated by limiting dilutions of MLC blasts. Clones displaying helper, suppressor, or cytotoxic functions (against Class I or Class II HLA antigens) were identified, using proliferative, 51Cr-release, and hemolytique-plaque induction assays. To determine whether functionally distinct clones share determinants that trigger the AMLC reaction we have tested the capacity of selected clones to cross-stimulate each other in secondary AMLC. Our data suggest that AMLC stimulatory determinants are related to common structure antigens of the T cell receptor for alloantigen, since helper clones, for example, (TLC #19) can induce memory responses to suppressor (TLC #209) as well as cytotoxic (TLC #207) clones and vice versa. The AMLC system seems well suited for studying network regulations within the T cell compartment.

B-Lymphocytes↗