Chagasic Patients Lack CD28 Expression on Many of Their Circulating T Lymphocytes

Abstract

A balanced host-parasite interaction during Trypanosoma cruzi infection allows for the establishment of a chronic infection that can last for many years. T cells are a major element responsible for parasite specific and non-specific immunity during the complex immune response of the host. However, the subpopulations of T cells involved in the response, as well as the exact mechanisms through which those cells are activated or rendered unresponsive, are not well defined. It is known that co-stimulatory signals, some of which are mediated via CD28, are of critical importance in the triggering of appropriate T cell responses. In this study the authors performed double-labelling studies to determine the frequency of expression of CD28 by CD4+ and CD8+ T lymphocytes in the peripheral blood of patients with Chagas' disease. The results show that chagasic patients throughout the spectrum of chronic clinical forms of the infection have significantly higher mean frequencies of CD4+CD28- and CD8+CD28-T cells, as compared with non-chagasic individuals. Considering the importance of CD28 for T-cell activation, the observed down-regulation or loss of CD28 during infection may indicate a possible basis for observed immunoregulatory events or distinct stages of T-cell activation in this infection. Recent evidence from patients with HIV/AIDS indicates that CD28- cell populations are more likely to undergo apoptosis, and increased apoptosis has been observed in experimental Chagas disease.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells

“…Prior studies on CD28 ¹ expansions did not take into account the HLA phenotype of the subjects under study [4][5][6][7][8][9][10]. Here we have shown that most of the CD8 þ CD28 ¹ T cell expansions were found in HLA-A3 þ patients.…”

“…They constitute a heterogeneous subset regarding phenotypic and functional properties. In spite of lacking the costimulatory molecule CD28, expansions of CD8 þ CD28 ¹ T cells are found in certain chronic disorders as well as in viral and parasitic infections [7][8][9][10]. The physiological significance of the expanded CD28 ¹ T cells remains unsolved however, since similar expansions can be found in healthy subjects [4][5][6].…”

Current concepts in immunoregulation and pathology of human Chagas disease

“…It has also been shown that CD8+ T cells from cardiac and digestive lesions express cytolytic molecules such as Granzyme or TIA-1 antigen [33 • ,35]. Adding to the importance of CD8+ T cells in chronic Chagas disease is the finding that a high percentage of these cells from chagasic patients lack CD28 expression, indicating chronic activation [40]. Albareda et al [41] also observed a high frequency of CD8+CD28− cells in chronic patients and suggested that these cells may be exhausted due to chronic antigenic restimulation.…”

Trypanosoma cruzi -Induced Activation of Functionally Distinct αβ and γδ CD4 − CD8 − T Cells in Individuals with Polar Forms of Chagas' Disease

“…It is caused by neuronal and cardiomyocyte damage, ultimately resulting in ventricular dilation and subsequent functional heart failure, which can lead to death (44). Cardiac patients display a T-cell-mediated inflammatory response in situ (13,24,41), which is responsible for the pathology; this inflammatory profile is also observed in circulating activated T cells found at high frequencies in these patients (2,16,19,32). Although it is clear that a plethora of parasite and host factors influences the clinical outcome of Chagas' disease, recent studies have suggested that activation of functionally distinct Tcell populations in T. cruzi-infected individuals may be responsible for the establishment of different clinical forms (17,20).…”