Does CD4+CD25+foxp3+ cell (Treg) and IL-10 profile determine susceptibility to immune reconstitution inflammatory syndrome (IRIS) in HIV disease?

Abstract

HIV-specific T-lymphocyte responses that underlie IRIS are incomplete and largely remain hypothetical. Of the several mechanisms presented by the host to control host immunological damage, Treg cells are believed to play a critical role. Using the available experimental evidence, it is proposed that enormous synthesis of conventional FoxP3 -Th cells (responsive) often renders subjects inherently vulnerable to IRIS, whereas that of natural FoxP3 + Treg cell synthesis predominate among subjects that may not progress to IRIS. We also propose that IRIS nondevelopers generate precursor T-cells with a high avidity to generate CD4+CD25+FoxP3+ Tregs whereas IRIS developers generate T-cells of intermediate avidity yielding Th0 cells and effector Tcells to mediate the generation of proinflammatory cytokines in response to cell-signaling factors (IL-2, IL-6 etc.). Researchers have shown that IL-10 Tregs (along with TGF-β, a known antiinflammatory cytokine) limit immune responses against microbial antigens in addition to effectively controlling HIV replication, the prime objective of HAART. Although certain technical limitations are described herein, we advocate measures to test the role of Tregs in IRIS.

HIV-Mycobacterium tuberculosisco-infection: a ‘danger-couple model’ of disease pathogenesis

“…Although IRIS is associated with certain infectious and non‐infectious conditions (Shankar et al ., ), the morbidity associated with HIV/TB co‐infection is significantly higher than for the other conditions. HIV‐infected patients with low CD4+ T‐cell counts ‘immunologically’ tolerate the presence of the tubercle bacilli as the host is unable to mount an inflammatory response (Shankar et al ., , b). Tuberculosis‐associated IRIS is considered critical in developing countries, where the proportion of HIV/TB IRIS is reportedly high, ranging from 10% to 43% (Breton et al ., ; Shelburne et al ., ; Murdoch et al ., ; Haddow et al ., ).…”

Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND

“…Chronic CNS-IRIS in HIV infected individuals may contribute to the development of HAND due to CNS damage caused by prolonged immune activation (reviewed in (Johnson and Nath 2011)). HIV infected individuals who do not mount an effective T reg response after cART initiation may be more prone to develop IRIS due to ineffectual suppression of hyperimmune responses after reconstitution of the immune system (Shankar et al 2008; Martin-Blondel et al 2012). During the chronic form of CNS-IRIS, elevated extracellular dopamine as a result of drug abuse may inhibit T reg function within the CNS, exacerbating this chronic immune activation and the development of HAND.…”

Tegumentary Leishmaniasis as the Cause of Immune Reconstitution Inflammatory Syndrome in a Patient Co-infected with Human Immunodeficiency Virus and Leishmania guyanensis

“…14 Additionally, it has been shown that numbers of naturally occurring Foxp3+ T regulatory cells are increased in patients in which IRIS does not develop, whereas patients in which IRIS develops normally elicit Th-0 cell and effector T cells responses, which produce pro-inflammatory cytokines in response to cellsignaling factors. 15 Our data show that the frequency of CD4 + CD25 + FOXP-3 + T cells in peripheral blood was low (1.82%) when compared with levels in healthy persons (5-10%). Therefore, although T regulatory cells were present, they were not sufficient to control establishment of ulcerated lesions or onset of systemic manifestations, which culminated in a comatose state.…”