What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery?

The T helper cell type 1 (Th1) response is essential to resist leishmaniasis, whereas the Th2 response favors the disease. However, many leishmanial antigens, which stimulate a Th1 immune response during the disease or even after the disease is cured, have been shown to have no protective action. Paradoxically, antigens associated with an early Th2 response have been found to be highly protective if the Th1 response to them is generated before infection. Therefore, finding disease-associated Th2 antigens and inducing a Th1 immune response to them using defined vaccination protocols is an interesting unorthodox alternative approach to the discovery of a leishmania vaccine.

Terminal maturation of resting B cells induced by macrophage factors

Mouse splenic macrophages from BALB/c nude mice (purified by plastic adherence) or cloned macrophage hybridomas stimulated with jacalin (12.5 microg/ml), a D-Gal binding lectin, produce one or more B-cell stimulatory factors which cause splenic B cells from BALB/c or C3H/HeJ mice to secrete immunoglobulin in a polyclonal manner as detected by reverse protein A plaque assays. Jacalin-stimulated macrophage supernatants (JacSup) activate both normal and Percoll gradient-purified small high-density (resting) B cells. Supernatants from total or resting BALB/c spleen cells cultured for 7 days in the presence of JacSup (derived from splenic BALB/c nude mice macrophages) were assayed for immunoglobulin isotypes by ELISA. Resting B cells produce only IgG3 and IgM, whereas total B cells secrete IgG3 and IgM as well as IgG1, IgG2a, IgG2b and IgA. Resting and total B cells from BALB/c nude mice are also stimulated by macrophage supernatants to secrete immunoglobulin, thus indicating that this activity is likely to be T cell independent. Moreover, jacalin-stimulated macrophage supernatants did not induce spleen cells or purified B cells to proliferate. Fractionation of factor-rich supernatants on a Sephacryl S-200 column revealed that the factor activity is located in fractions corresponding to a molecular mass of 25-27 kDa. Taken together, these results suggest that upon the action of a macrophage factor(s) resting B cells undergo terminal differentiation without proliferation in the absence of T cells.

Potent stimulation of murine B cells to proliferate and to secrete immunoglobulins by a lipoteichoic acid-like molecule produced by Clostridium botulinum C and D

Bacterial products have served as important immunological tools to study ly,phocyte activation. The lipopolysaccharides of the Gram-negative bacteria are well known to be potent activators of B lymphocytes. Several Gram-positive bacteria produce exotoxins that are superantigens for T cells. In the present study, we demonstrate that the Gram-positive bacteria Clostridium botulinum C and D produce a high molecular weight mitogen (Cb mitogen) that is a potent activator of murine B lymphocytes. The Cb mitogen was discovered as a consequence of our attempt to investigate a possible superantigen activity present in the botulinum exotoxins. We observed initially that mouse spleen cells were strongly stimulated to proliferate by culture supernatants of C. botulinum C and D. However, the characterization of the responding cell ruled out superantigen because only the B lymphocytes were stimulated to proliferate and to secrete immunoglobulins, and they did so independent of T cell help. In addition, the molecular characterization of the Cb mitogen demonstrated that the purified botulinum toxin was devoid of mitogenic activity. In contrast, the fractionation of the culture supernatant of C. botulinum C in an FPLC Superose 12 column indicated that the Cb mitogen was present in the void volume of the column (MW ò 300 kDa) which had no toxigenic activity. However, the fractions containing molecules of 150 KDa were highly toxic for mice and had no mitogenic activity...

Immune evasion by Trypanosomatidae: normal aggregated immunoglobulin protects against lysis by the alternative complement pathway

Immunoglobulin Fc receptors (FcRs), present in Trypanosomatidae pathogenic for mammals, may be a mechanism by which these parasites escape the host immune response. We studied the possible role of these receptors in evasion by the alternative complement pathway. Promastigotes of Leishmania amazonensis and trypsinized trypomastigotes of Trypanossoma cruzi treated with heat-aggregated normal gamma globulin and then incubated with fresh normal guinea pig serum were shown to be more resistant to lysis. When compared to log phase Leishmania promastigotes, this resistance was at least 4.5-fold greater in parasites harvested in the stationary growth phase EDTA and egta PLUS MgCl2 inhibited the cytotoxic effect of serum, suggesting the participation of the alternative complement pathway. The distribution of FcRs among genera of Trypanosomatidae that arepathogenic, infective or noninfective for mammals and their affinity for mammalian and fowl immunoglobulin were also examined. These receptors ara presented only in species infective or pathogenic for mammals, a finding that suggests that this structure is essential for the establishment of infection but in not necessarily a virulence factor. Further more, the ligand specificity is limited to the immunoglobulin of mammalian but not of fowl origin

Synergistic signal of an anti-hamster T cell monoclonal antibody on antigen-induced T cell proliferation

1.The use of monoclonal antibodies (mAb) has permitted the identification of T cell surface antigens and the classification of these antigens based upon phenotype and function. Some of these monoclonal antibodies can identify antigens specifically involved in T lymphocyte activation and are also able to induce, under certain conditions, T cell proliferation. 2. We describe a new mAb raised against hamster T cells which binds to a 45-KDa cell surface antigen expressed on 45% of thymic cells and 90% of mature T lymphocytes. This mAb,d esignated X2VA, alone does not cause T cells proliferation, but increases in a synergistic manner T cell proliferation when these cells are cultured in the presence of specific antigens, or used in mixed lymphocyte reactions. 3. When the X2Va mAb is used as single signal for the T cells it induces the production of a T cell growth factor, suggesting that the synergist effect observed during antigen-induced T cell proliferation is mediated by one more cytokines. 4. Our results indicate that the X2Va mAb recognizes an antigen which is expressed during T cell ontogenesis and which is involved in hamster T cell Activation