Molecular correlates in AIDS patients following antiretroviral therapy: diversified T‐cell receptor repertoires and in vivo control of cytomegalovirus replication

Abstract

An important degree of molecular and functional immune recovery is possible in end-stage AIDS patients introduced to therapy. Diversification of TCR repertoires and the in vivo restoration of immunocompetence to control opportunistic infections clearly show that an important degree of molecular immune reconstitution is established following the initiation of ART even in late-stage AIDS.

Immune reconstitution disease associated with parasitic infections following antiretroviral treatment

“…A switch from type 2 to type 1 cytokine profiles in T lymphocyte stimulation assays and in tissues is detectable early in treatment, with increases in IFN‐γ and IL‐2 production in response to antigen (25,26). There is diversification of the pathogen‐specific T cell receptor repertoire (27,28) and delayed‐type hypersensitivity responses to antigens assessed by skin testing are restored (24,29).…”

“…CD8 activation (as determined by co‐expression of CD38 and HLA‐DR) decreases during ART (4,16,22), probably reflecting to a large extent the reduction in HIV‐specific CD8 response that accompanies the reduction in antigen load (42). However, CD8‐mediated responses to CMV, for example, improve in the context of an expanding T cell repertoire (28), an effect which appears CD4 cell dependent (43).…”

TCR Spectratyping in Transplantation

“…For example, testing of the Vβ repertoire is regarded as an indicator for the immunocompetence in patients that underwent hematopoietic stem cell transplantation or in patients with HIV infections. 8,9 The T-cell receptor repertoire will be skewed on infection, as pathogen-specific T cell clones will be expanded, thus dominating others. Second, the skewing of the TCR can occur upon antigen challenges as antigen-specific T-cell clones will expand more rapidly.…”