Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes.

Abstract

To compare the helper function of murine T cell clones that secrete IL-2 and IFN-gamma (Th1 cells) or IL-4 and IL-5 (Th2), purified resting B cells were stimulated with F(ab')2 rabbit anti-mouse Ig (RAMG) and rabbit Ig-specific, class II MHC-restricted cloned T cells belonging to the two subsets. Both Th2 clones examined induced strong proliferative responses of B cells in the presence of RAMG, as well as the secretion of IgM and IgG1 antibodies. In contrast, the Th1 clones tested failed to stimulate B cell growth or antibody secretion. Th2-mediated B cell activation was dependent on IL-4 and IL-5, and was also inhibited by IFN-gamma or IFN-gamma produced by Th1 cells present in the same cultures. However, the failure of Th1 cells to help resting B cells could not be reversed with neutralizing anti-IFN-gamma antibody. In addition to this inhibitory effect, IFN-gamma was required for the secretion of IgG2a antibody, particularly when B cells were stimulated with polyclonal activators such as LPS. Finally, both sets of T cell clones secreted lymphokines when stimulated with purified B cells and RAMG. These experiments demonstrate that T cells that differ in lymphokine production also differ in their ability to help B cells as a result of cognate interactions at low concentrations of antigens. Moreover, IL-4, IL-5, and IFN-gamma serve different roles in the T cell-dependent proliferative and differentiative responses of resting B lymphocytes.

Th1 and Th2 CD4+ T Cells Provide Help for B Cell Clonal Expansion and Antibody Synthesis in a Similar Manner In Vivo

“…Although early in vitro studies indicated that both Th1 and Th2 cells could support B cell responses (15)(16)(17), the capacity of Th1 cells to provide cognate help for B cells is controversial, with some studies reporting that they are relatively deficient in this function (21,39,40). However, care must be taken when interpreting such in vitro studies, as examination of several Th1 and Th2 clones revealed considerable variation in their ability to help B cells with some Th2 clones failing to support Ab synthesis at all (15).…”

Collagen‐induced arthritis in an outbred group of rhesus monkeys comprising responder and nonresponder animals. Relationship between the course of arthritis and collagen‐specific immunity

“…In this respect, IL-4, IL-6, and interferon-y (IFNy) may be important lymphokines. It is known that IL-4 plays a role in immunoglobulin isotype switching (27), and that it can inhibit IgM secretion in vitro (28). IL-6, which was found at high levels only in the arthritic monkeys, is a cytokine that, in vivo, can induce polyclonal B cell activation and autoantibody production (29).…”

Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen

“…A similarly balanced IgG1: IgG2a ratio was observed following delivery of OVA and CpG DNA (0.5). These results suggest that VRP co-delivery significantly alters the systemic IgG subtype profile compared to delivery of antigen alone, and results in a balanced antibody response with the production of both Th1 and Th2 IgG antibodies [34,35]. The antibody adjuvant data presented here and in Thompson et al [29] were derived from experiments performed in Balb/c mice; however, we have observed significant antibody adjuvant activity in several mouse strains including Balb/c, C57BL/6, and 129 Sv/Ev, suggesting that the VRP adjuvant effect is not dependent upon a specific mouse genotype (Thompson J.M.…”