Paola Marelli

B and T lymphocytes regulated by idiotype anti-idiotype interactions inhibit delayed-type hypersensitivity to BCG in mice

Mice infected subcutaneously with 2 X 10(7) CFU of Mycobacterium bovis strain BCG (BCG) were able to mount a specific DTH response, whereas mice infected intravenously with the same dose of microorganisms were not. The suppression turned out to be mediated by id+ anti-PPD B lymphocytes, which arose very early during the infectious process and induced anti-id B lymphocytes. These cells were found at Day 4 after infection and exerted their effect by activating antigen-specific suppressor T lymphocytes, which affected the efferent phase of the DTH response. These results clearly indicate that the activation of a complex immunosuppressive circuit represents a mechanism by which BCG may interfere with the hosts immune response already during the very early phases of infection.

Staphylococcus aureus-induced suppression of contact sensitivity in mice: Suppressor cells elicited by polyclonal B-cell activation are regulated by idiotype-anti-idiotype interactions

Staphylococcus aureus strain Cowan I, a strong polyclonal B-cell activator (PBA), inhibited contact sensitivity to oxazolone in mice when administered 24 hr before sensitization. This suppression was mediated by idiotype-positive (Id+) B lymphocytes, which arose very early during the sensitization process and induced anti-Id B cells. These cells were found at Day 3 of the sensitization process and exerted their effect by activating antigen-specific suppressor T lymphocytes, which affected the efferent phase of the immune response. S. aureus strain Wood 46, which lacks of the ability to act as a PBA, was unable to inhibit contact sensitivity. These results indicate that PBA may play an important role in the regulation of cell-mediated immune reactions.

BCG-activated NK cells regulate the antibody response to SRBC and restore immune reactivity to PPD in BCG-infected mice

C57B1/6 mice show a significant increase in the number of natural killer (NK) cells in the peritoneal cavity, four days after intraperitoneal infection with Mycobacterium bovis strain BCG. Cell transfer experiments demonstrated that BCG-induced NK cells are able to depress the induction of antibody response to an unrelated antigen (i.e., sheep red blood cells) in recipient mice. The involvement of macrophages, B and T cells in the phenomenon was ruled out by using different purification steps. In addition, BCG-induced NK cells were shown to be able of partially restoring the DTH response to PPD in recipient mice that were anergic to the latter antigen as a consequence of intravenous infection with large doses of BCG.

Depression of the immune responsiveness in mice treated with thioacetamide after antigen exposure

The effects of the weak carcinogen thioacetamide (TAA) on the mouse immune response have been investigated. TAA administration up to 1 day after antigen priming markedly suppressed the antibody response to both T-dependent (sheep erythrocytes) and T-independent (trinitrophenyl-Ficoll) antigens; the compound was ineffective when given 3 or 4 days after immunization. A significant suppression of the in vitro lymphoproliferative response to the B-cell mitogen S. aureus Cowan I was evident from 3 to 48 h after TAA treatment. On the other hand, cell-mediated immune response to oxazolone was suppressed by TAA at each time tested, including that of challenge. The in vitro lymphoproliferative response to concanavalin A was decreased 12 h after TAA administration only, when adenosine deaminase activity within lymphocytes was increased. Furthermore, TAA is endowed with anti-inflammatory activity, as shown by the decreased footpad swelling and by evaluation of the inflammatory cell infiltration upon carrageenan injection. Taken together, these findings suggest selective TAA interaction with multiple targets within the immune system, including B- and T-lymphocytes, while non-specific cytotoxicity can be reasonably ruled out, since hematological determinations and phenotypic analysis of spleen lymphocyte subsets showed no relevant changes.

B-cell-mediated depression of the granulomatous response to BCG in mice

The depression of the granulomatous response to Mycobacterium bovis strain BCG in mice infected intravenously with 2 x 10(7) CFU of the microorganism turned out to be mediated by various types of cells arising at different times after infection. Anti-PPD B lymphocytes were found to play a major role at Day 1 after infection and to be no longer effective 4 days later. At this time the depression was mediated by anti-idiotype B lymphocytes, whereas T lymphocytes proved to be involved in later phases of the infectious process. These results show that B lymphocytes may be of critical importance in the regulation of cell-mediated immune reactions to this facultative intracellular parasite.

Polyclonal B Cell Activators Inhibit Contact Sensitivity to Oxazolone in Mice by Potentiating the Production of Anti-Hapten Antibodies that Induce T Suppressor Lymphocytes Acting through the Release of Soluble Factors

Polyclonal B cell activators (PBAs) such as purified protein derivative, lipopolysaccharide, Staphylococcus aureus strain Cowan I (StaCwI), and Pseudomonas aeruginosa inhibit contact sensitivity to oxazolone in mice when given 24 h before sensitization. This suppression, transferable from immunodepressed animals to oxazolone-sensitized recipients with immune serum, has been shown to be due to the early appearance of anti-hapten antibodies. These antibodies elicit T suppressor cells which release soluble factor(s) capable of inhibiting the passive transfer of contact sensitivity.

Effects of Pseudomonas aeruginosa on Immune Functions

The ubiquitous distribution of Pseudomonas aeruginosa contrasts with its limited colonizing potential for healthy individuals. Despite the fact that P. aeruginosa is able to produce a large variety of virulence factors, this microorganism undoubtedly remains an opportunistic pathogen that can infect and eventually cause disease only in patients with defects in local or systemic immunity.

Role of B Lymphocytes and Antibodies in the Regulation of Cell-Mediated Immune Reactions to BCG in Mice

The mechanisms underlying the depression of the specific cell-mediated immune (CMI) reactions during the course of active tuberculous infections are complex and far from being fully understood. As comprehensively discussed in other chapters, in spite of considerable research, a clear picture is still lacking.