Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

Abstract

A B S T R A C T We have recently noted marked differences between the in vitro responses of human B lymphocytes to stimulation with soluble antigens vs. stimulation with mitogens. In the present study, these differences were analyzed in terms of the precursor frequencies for the T cells and B cells involved and in terms of the radiation sensitivity of the T cells providing help in the two systems. Marked differences were found between antigen-induced and mitogen-induced systems with regard to T cell precursor frequencies and radiation sensitivity. In contrast, the precursor frequencies for the B cells involved in the two systems were approximately the same. In addition, having developed a system for the study of human antigen-specific B cell responses, we were interested in delineating the nature of the allogeneic effects that might be operative in this system. Marked allogeneic effects, both positive and negative, were noted in this system and will need to be taken into account in any studies that try to address the question of the genetic restriction, if any, that exists in human antigen-specific T cell-B cell collaboration.Appreciation of the marked differences between the antigen-specific and mitogen-induced activation and immunoregulation of human B cell responses will be of importance in understanding the relationship between specificity and nonspecificity of antibody production in normal and disease states. INTRODUCTIONT cell regulation of B cell reactivity is an area of major interest and importance in both animal and human systems. With the recent availability of several systems Address all correspondence to Dr. H. Clifford Lane. Received for publication 20 January 1983 and in revised form 30 March 1983. to study human B cell function in vitro, considerable interest has centered around the precise nature of the T cell regulation of human B cell responses in both polyclonal and antigen-specific assay systems. Unfortunately, there have been conflicting data among sev-. eral of these systems (1-10). Of particular note has been the divergence of results with regard to the radiosensitivity of T cell help and the relative contributions of allogeneic effects in the mitogen-induced vs. antigen-induced human B cell systems. Disagreement with regard to this latter point has led to difficulty in delineating the precise nature of genetic restrictions in T cell-B cell collaboration in antigen-specific responses as well in appreciating the scope of allogeneic effects in co-culture experiments now commonly used in the study of patients with immunemediated or immunodeficiency diseases.Recently, in vitro systems have been developed for the study of antigen-induced, antigen-specific antibody production and secretion into culture supernatants by human B cells (11)(12)(13)(14). The use of enzymelinked immunosorbent assays (ELISA)l has proven to be extremely useful in these studies because of their simplicity, sensitivity, and specificity. These advances have allowed for a more precise study of the mechanisms involved in...

Cooperation between major histocompatibility complex mismatched mononuclear cells from a human chimera in the production of antigen-specific antibody.

“…This may be attributed to the fact that PWM and TT induce the activation of different populations of cells, and that the frequency of cells able to respond to PWM is higher than that able to respond to Ag. A comparable difference in frequence has been described for antigen-specific precursor T cells by Lane et al (18). Such a difference may also exist at the level of recirculating memory B cells (19).…”

Clonal analysis of T lymphocytes in the acquired immunodeficiency syndrome. Evidence for an abnormality affecting individual helper and suppressor T cells.

“…In each of three separate experiments, cells from one healthy male homosexual and one healthy heterosexual donor were studied. Heparinized peripheral blood was obtained from the healthy subjects, however, because of the severely decreased numbers of circulating helper T cells in the patients with AIDS (Table I), peripheral blood Iymphocytes from these patients were obtained in large numbers (200-40 X 106) by manual plasmapheresis (25). Mononuclear cells were separated by density gradient centrifugation on Hypaque-Ficoll (26), and purified T cells were obtained by rosetting mononuclear cells with sheep erythrocytes coated with 2-aminoethylisothiouronium as described (27).…”

Beryllium Skin Patch Testing to Analyze T Cell Stimulation and Granulomatous Inflammation in the Lung

“…In contrast, memory CD4 ϩ T cells specific for tetanus toxoid or purified protein derivative of Mycobacterium tuberculosis in healthy individuals occur at a frequency of 1 in 5,000 to 1 in 100,000 CD4 cells (40). Estimates of Th cell precursor frequency in the blood following injection of a conventional Ag like keyhole limpet hemocyanin ranged from 1 in 100,000 to 1 in 800,000 (41).…”