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The HIV-1 gp120 recombinant protein fragment encompassing aa residues 410-511, that contains the CD4 binding region (rp120cd), and fragment aa 446-511, which lacks the sequence responsible for CD4 binding (rp120), were synthesized to study their ability to induce TNF synthesis in human monocytes. The rp120cd stimulated TNFα secretion by monocytes while the rp120 and full-length recombinant protein (FL gp120), used as control, failed to do so. However, FL gp120 stimulated peripheral blood mononuclear cells (PBMC) and lymphocytes for TNF production and this was inhibited by anti-CD4 MAb. The rp120cd also caused TNF secretion by PBMC that was not blocked by this antibody. Furthermore, FL gp120 but not rp120cd inhibited anti-CD4 mAb binding to CEM cells. Hence, FL gp120 may cause TNF release from lymphocytes by binding to CD4, while rp120cd interacts with monocytes but not lymphocytes and induces TNF production by a mechanism not involving CD4 binding. Unexpectedly, FL gp120 but not rp120cd stimulated IL-6 secretion and IL-6 mRNA synthesis in monocytes. The FL gp120-induced production of IL-6 by monocytes was inhibited by anti-CD4 monoclonal antibody (MAb). Thus, there may be different requirements for TNF induction in lymphocytes and monocytes stimulated with various preparations of gp120 and for the selective induction of cytokines in monocytes. The enhanced production of TNF in HIV infection and AIDS may involve distinct cellular sources and different mechanisms.

FcR+ and FcR- monocyte subsets were added to the pokeweed mitogen (PWM) or Staphylococcus aureus Cowan I-stimulated cultures of peripheral blood mononuclear cells (PBMC) or to PBMC depleted of monocytes. The numbers of immunoglobulin-secreting cells (ISC) and cells with intracytoplasmic immunoglobulins (PC) were evaluated 6 days later. The addition of FcR- subset increased the number of ISC in cultures of PBMC stimulated with PWM and reconstituted the response of monocyte depleted PBMC. In contrast, FcR+ monocytes suppressed PWM-induced response and, when added in high dose, also that induced by S. aureus. The FcR+ monocytes suppressed the response by inhibition of immunoglobulin secretion but not the development of PC. This suggests that FcR+ monocytes may modulate humoral response by preferential inhibition of the final differentiation of B lymphocytes into ISC.

In coculture experiments with normal lymphocytes, peripheral blood lymphocytes (PBL) of 10 boys with hypogammaglobulinemia were screened for the presence of cells able to suppress Pokeweed mitogen (PWM)- and Staphylococcus aureus Cowan I-induced immunoglobulin production in vitro . PBL and T lymphocytes of two patients were shown to suppress reproducibly PWM-induced immunoglobulin production of control PBL and of control B + T lymphocytes. PBL of three other patients were also able to suppress but their activity was expressed only in combination with some but not other normal lymphocytes. In neither case was the Cowan I-induced response suppressed. PBL and T lymphocytes of one other patient were able to suppress both PWM- and S. aureus Cowan I-induced immunoglobulin production of normal lymphocytes. These data provide evidence for two functionally distinct suppressor T lymphocytes in hypogrammaglobulinemic patients.