Search

The in vitro induction of an ovalbumin-specific human T cell suppressor factor is described (TsF120-OA). The antigen-specific suppressive component can be purified by affinity chromatography from supernatants derived from Marbrook-Diener type cultures of peripheral blood T cells stimulated with a high dose of ovalbumin. TsF120-OA suppresses the antigen-induced PFC formation of human blood B cells in vitro in an antigen-specific way. The target of TsF120-OA activity is shown to be the T helper cell. No genetic restriction in the action of the factor is observed.

Some immunochemical characteristics of a T-cell-derived ovalbumin (OA) antigen-specific helper (ThF120-OA) and a corresponding OA-specific suppressor effector factor (TsF120-OA) are described. These immunoregulatory molecules are retained by columns containing either the insolubilized antigen OA or the lectin ConA, or antibodies specific for the VH-region of immunoglobulins, for the beta 2-microglobulin or for Ia-framework determinants. Neither the helper factor nor the suppressor factor showed affinity for antisera specific for immunoglobulin isotypes. In search of a constant-region-like structure in factor molecules, antisera were raised in rabbits using ThF120-OA and TsF120-OA. The results show that antisera raised against ThF120-OA recognize one or more determinants of different antigenic specificities common to human ThF. This common structure is not species-specific since it is also recognized by rabbit antisera to mouse helper factor. It is absent, however, on human TsF120-OA. In the same way, human TsF120-OA was shown to interact with rabbit antisera to human (or murine) suppressor factors of different antigenic specificities, but not with anti-ThF.

We intended to investigate whether the suppression of antigen-induced antibody responses in vitro in man by T suppressor cells required contact of T suppressor cells with target cells or whether this effect was mediated by factors released by T suppressor cells. To this end supernatants of antigen-induced T suppressor cells were tested (by a plaque forming cell assay) for their capacity to suppress antibody responses of autologous and allogeneic human peripheral blood lymphocytes. We have shown that supernatants of antigen-specific T suppressor cells, designated as TsF24: a) can suppress an antibody response of autologous but not allogeneic lymphocytes to the inducing antigen; b) are antigen-specific in their effect; and 3) are produced by radiosensitive T cells. Furthermore, the target of the factor is a radiosensitive T cell. These findings taken together indicate that, in the generation of T-effector suppressor cells in man, T-T interactions occur, and in addition, that cellfree factors may be involved in these interactions.

Suppression of an antigen-specific plaque-forming cell response of human blood lymphocytes can be effected by T mu+ cells that have been primed previously by antigen in vitro for 6 days. While lacking the capacity to suppress the plaque-forming response directly, these primed T mu+ suppressor-inducer cells stimulate a subpopulation of unprimed T mu gamma- cells to differentiate to T gamma + suppressor-effector cells. The T mu+, T gamma+ and T mu gamma- subsets have been shown to be heterogeneous populations of cells. Therefore, the functionally defined T suppressor-inducer, -precursor and -effector cells were characterized by OKT monoclonal antibodies and by the capacity to form rosettes with autologous erythrocytes (ar+). Evidence will be presented that in vitro a T4+mu+ar- cell induces a T8+mu gamma-ar+ precursor cell to differentiate to a T8+gamma+ar- suppressor-effector cell. A similar T suppressor-effector cell can also be isolated directly from peripheral blood of normal donors.

The investigation described here is concerned with the T cell regulation of the antigen-specific antibody response which has been studied in patients suffering from systemic lupus erythematosus (SLE). Apart from the fact that T helper cell activity was found to be less efficient, it appeared that the peripheral blood leucocytes (PBL) of patients in an active stage of the disease did not contain the suppressor precursor cells, which functions as the target cell for the inductive signal of T mu+ suppressor inducer cells. The absence of the suppressor precursor cells in SLE patients coincided with the absence of T gamma+ suppressor effector cells. Characterization of the (post-thymic) precursor cells (derived from normal donors) with the aid of monoclonal antibodies of the OKT series and several other markers pointed out that this population contains OKT4+ as well as OKT8+ cells. Further experiments demonstrated that the cells are capable of rosetting with autologous erythrocytes, and do not bear Fc receptors for IgM or IgG. Considering the various findings as a whole the conclusion is warranted that the post-thymic suppressor precursor T cell can differentiate into a suppressor effector cell only after interaction with T suppressor inducer cells.

The in vitro induction and assay of an ovalbumin-specific human T cell helper factor are described. Peripheral blood T cells, cultured with ovalbumin in a Marbrook-Diener system, produce an antigen-specific factor(ThF120-OA), which can be purified by affinity chromatography. The in vitro studies with ThF120-OA pointed out that in the production of the factor as well as in the factor-B cell interaction the adherent cell determines the genetic restriction. The results of kinetic studies on T helper activities demonstrated that Thf120-OA provides an auxiliary activity at various moments during the differentiation of the human peripheral B cell into an antibody-secreting cell. The observed differences in the mode of action of Th cells and Th factor are discussed.

The present study documents the relationship between the development of rubella vaccine-associated arthropathy and isotype-specific rubella antibody responses in a prospectively studied population of 44 adult rubella hemagglutination inhibition (HAI) seronegative females undergoing rubella immunization. Rubella-specific IgM, IgG, and IgA antibody responses were evaluated prior to and at 1, 2, 3, 4, 5, 6, 12, and 24 weeks postvaccine. Detectable preimmunization rubella antibody of the IgG or IgA class was present using ELISA techniques in 6 of 6 individuals developing acute arthritis, 13 of 17 developing acute arthralgia, and in 15 of 21 with no joint manifestations postvaccine. Significantly elevated HAI IgM responses were noted 3 and 4 weeks postvaccine in the acute arthritis group but no significant differences were found in IgG and IgA rubella antibody levels postvaccine in relation to the presence or absence of joint manifestations at any time period postvaccine. The data support rubella reinfection as an important feature of rubella vaccine-associated arthropathy but do not support a role for quantitative differences in rubella IgG and IgA antibody in the pathogenesis of this syndrome.

Six women developed chronic long-term arthropathy after postpartum immunization against rubella. All individuals developed acute polyarticular arthritis within 12 days to three weeks postimmunization and have had continuing chronic or recurrent arthralgia or arthritis for two to seven years after vaccination. Acute neurological manifestations, consisting of carpal tunnel syndrome or multiple paresthesiae, developed postvaccination in three women. Two have developed continuing active or chronic recurrent episodes of blurred vision, paresthesiae, and painful limb syndromes together with recurrent joint symptoms. Chronic rubella viremia has been detected in peripheral blood mononuclear cell (MNC) populations in five of the six women up to six years after vaccination. In addition rubella virus was isolated from breast milk MNCs in one individual at nine months postvaccination and from peripheral blood MNCs in two of four breast-fed infants studied at 12-18 months of age. Immune responses to rubella virus studied at sequential intervals after vaccination correlated with development of rheumatologic and neurological manifestations.