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We have developed a visual microtiter assay to detect solubilized cell-surface antigens which react with monoclonal antibodies. The assay depends on the ability of adsorbed monoclonal antibody to bind target cells to microtiter V wells, and the inhibition of binding by antigen. We have used this assay to follow a 600-fold purification of the human lymphocyte differentiation antigen 3A1 extracted from HSB-2 cells. Antigen 3A1 is a glycoprotein with a molecular weight of approximately 40, 000 daltons.

A variety of immunologic mechanisms may theoretically give rise to disease in the salivary glands. Among them are abnormal antibody production, hyper-reactive T-lymphocytes, and mono- or oligoclonal expansions of B-lymphocytes, While it is not clear which, if any, of these mechanisms are of prime importance in the immunopathology of salivary gland disease, they provide a framework, within which to discuss theoretical approaches to the treatment of autoimmune salivary gland disease. Among the techniques used to decrease antibody-induced damage are non-steroidal anti-inflammatory agents, plasmapheresis, and corticosteroids. Cyclosporin, monoclonal antibodies, and biologic response-modifiers may be used to modulate T-cell function, and anti-idiotype antibodies or immunosuppressive agents may be used to treat malignant expansions of B-cells. Although the generally benign nature of autoimmune salivary gland disease precludes the use of many of the potentially toxic treatment regimens discussed here, the appreciation of these approaches to immunomodulation provides a basis upon which to develop new and innovative therapeutic strategies.

Two of the major immunosuppressive agents used in clinical practice are corticosteroids (CS) and the cytotoxic agents. Cytotoxic agents such as cyclophosphamide (CY) when used as immunosuppressive agents result in a dosedependent decrease in the circulating peripheral leukocyte count. In addition, selective functional inhibition can be demonstrated following treatment with CY. In serial studies with patients receiving chronic low-dose (2 mg/kg/day) CY therapy, selective suppression of B cell function with a relative sparing of helper and suppressor T cell function for antibody production was noted. In vivo administration of CS resulted in multiple and heterogeneous effects on human mononuclear cell traffic and function with a profound and transient depletion of monocytes and lymphocytes from the circulation. There was a selective depletion of T cells versus B cells, and within the T cell pool, selective depletion of immunoglobulin class M Fc receptor-bearing T cells was seen. With regard to functional capabilities, in vitro and in vivo exposure of lymphoid cells to CS resulted in a suppression of T cell and B cell proliferation with a relative sparing of B cell differentiation with in vitro CS. Suppressor T cell as opposed to helper T cell function was selectively sensitive to CS. Thus, these studies demonstrate the multifaceted and diverse effects of CS and CY on human lymphoid responses and may shed light on the mechanisms of clinical effect of these agents.

Since June and July of 1981 when the Centers for Disease Control (CDC) initially reported the occurrence of 5 cases of Pneumocystis carinii pneumonia and 26 cases of Kaposi’s sarcoma in previously well homosexual men (CDC, 1981), there has literally been an explosion in the numbers of new cases of this devastating syndrome that we now recognize as the acquired immunodeficiency syndrome or AIDS. By May 1984 more than 4,400 cases of AIDS, occurring in 46 states and the District of Columbia, had been reported to the CDC (CDC weekly surveillance report on AIDS). Moreover, at least 700 cases had been documented in at least 33 countries outside of the United States (CDC, unpublished statistics).

Publisher Summary Assays for mitogen (PHA) induced cellular cytotoxicity (MICC) and antibody dependent cellular cytotoxicity (ADCC) against 51-chromium labeled chicken red blood cell (CRBC) targets are performed with mononuclear cells from the peripheral blood (PB) and bone marrow(BM) of normal humans. Mononuclear cell suspensions are obtained from PB by Hypaque-Ficoll separation and from BM by sucrose density gradient centrifugation. Cytotoxicity is measured by isotope release from labeled CRBC targets in the presence and absence of either PHA or various dilutions of rabbit anti-CRBC antiserum. Purified suspensions of polymorphonuclear leucocytes (PMNs) obtained from PB by dextran sedimentation of the erythrocyte-PMN button following Hypaque-Ficoll separation as well as suspensions of BM cells highly contaminated with PMNs are both highly efficient in killing in both the MICC and ADCC assays. Removal of adherent cells does not significantly change the degree of maximal MICC or ADCC. The relative efficiencies of the PB and BM in mediating MICC and ADCC may reflect the relative proportions of various lymphoid cell populations in those compartments. This chapter discusses that human BM contains mononuclear cell populations with functional capacities characteristic of mature immunocompetent cells.

Although effective therapies are available for many of the infections and tumors that occur in patients with the acquired immunodeficiency syndrome (AIDS), no therapy exists for the underlying immunodeficiency. Three approaches used to treat this immunodeficiency have included wholescale immune replacement through lymphocyte transfers, bone marrow transplantation, and thymic implantation; immunologic enhancement with biologic-response modifiers, such as gamma interferon, interleukin-2, and some drugs; and antiretroviral therapy. Because of the persistence of the etiologic virus, both immune replacement and enhancement will probably be ineffective unless effective strategies are developed against the virus. Agents that have shown antiviral activity in vitro which are currently in clinical trials include suramin, heteropolyanion-23 (HPA-23), ribavirin, and alpha interferon. Foscarnet and monoclonal antibodies have yet to enter clinical trials in the United States. It is still too early to tell if any of the antiviral agents will prove of value in the management of patients with AIDS.