Self and Nonself Stimulatory Molecules Induce Preferential Expansion of CD5⁺ B Cells or Activated T Cells of Chagasic Patients, Respectively

Abstract

It has previously been demonstrated that Trypanosoma cruzi-derived antigens (TRP) and human parasitespecific antibodies (Id) stimulate proliferation of cells from Chagasic patients. More recently, we have shown that activated T cells and CD5 þ B cells are present in elevated levels in the peripheral blood of Chagasic patients. Upon in vitro exposure to these two different types of stimulatory molecules (TRP, Id), we now show that each of these elevated populations respond differentially to TRP or Id. We found that stimulation with TRP led to preferential expansion of activated T cells, while Id preferentially stimulated CD5 þ B cells and CD8 þ T cells. Moreover, this expansion of CD5 þ B cells by Id was even more pronounced in cultures of cells from Chagasic patients with the severe, cardiac form of the disease, as compared to indeterminate patients. CD8 þ T cells comprise approximately 50% of the total T cells in cultures stimulated by Id while in TRPstimulated cultures their frequency is proportionally lower. Since parasite antigens and antiparasite antibodies are always present in the host during the chronic phase of the disease, they may also be involved with differential activation mechanisms of these cell populations in vivo.

Monocytes from Patients with Indeterminate and Cardiac Forms of Chagas' Disease Display Distinct Phenotypic and Functional Characteristics Associated with Morbidity

“…This hypothesis could represent an important mechanism of controlling inflammatory reaction in indeterminate patients, where a lower inflammatory response would lead to less tissue damage, which is consistent with this form of the disease. We have previously observed a slightly lower proliferative response of CD4 ϩ T cells from indeterminate-disease patients, compared to cardiac-disease patients, on stimulation with parasite antigens (11). Although those differences were not statistically significant, they may be indicative of lower antigenic presentation to CD4 ϩ T cells in indeterminate-disease patients as a result of lower HLA-DR expression.…”

“…Many studies have attempted to determine the stimuli responsible for T-cell activation in human Chagas' disease. Parasite-derived antigens are able to stimulate CD4 ϩ and CD8 ϩ T cells from Chagas' disease pa-tients in vitro (11). Moreover, T cells that can recognize and proliferate in response to autologous antigens have also been detected in Chagas' disease patients (8,17).…”

Trypanosoma cruziInfection Induces Differential Modulation of Costimulatory Molecules and Cytokines by Monocytes and T Cells from Patients with Indeterminate and Cardiac Chagas' Disease

“…While parasiterelated factors may influence the development of different clinical forms (45), it is clear that the host's immune response, especially T cells, is critical in the development of pathology in experimental models (44) as well as in human disease (12). T cells act through the production of cytokines (6,10,17) and as mediators of tissue destruction in Chagas' disease (22,34). Previous studies have evaluated the role of costimulatory molecules in murine infection with T. cruzi.…”

Pathogenesis and Pathology of Chagas' Chronic Myocarditis

“…These results were similar for both indeterminate and CCC patients. Moreover, activated T cells lacking the co-stimulatory molecule CD28 are increased in chagasic patients and express high levels of HLA-DR molecules (Dutra, et al, 2000). Some interesting differences were demonstrated between indeterminate and CCC patients.…”