The human B cell response to T cell independent type 2 antigens is regulated by thymus-derived lymphocytes. We analyzed the role of T cells in the in vitro antibody response to type 4 pneumococcal polysaccharide (PS4). We here show that the amplifying effect of T cells, which has previously been shown to be radioresistant and confined to T cell preparations enriched for CD4+ cells, is MHC non-restricted as demonstrated in cultures carried out in the presence of allogeneic T cells. Also, T cell clones derived from non-related donors are able to enhance the B cell response to PS4. All TCR alpha beta +, CD 4+ T cell clones, but none of the TCR alpha beta +, CD 8+ T cell clones tested, enhanced the B cell response to PS4. Furthermore, 3 out of 6 TCR gamma delta+ T cell clones were capable of enhancing the anti-PS4 B cell response. Experiments using recombinant lymphokines and glutaraldehyde-fixed T cells indicated that both lymphokines and T-B cell interactions are required for an optimal antibody response to PS4.