Persistent Anti-Gag, -Nef, and -Rev IgM Levels as Markers of the Impaired Functions of CD4+ T-Helper Lymphocytes During SIVmac251 Infection of Cynomolgus Macaques

Abstract

This study analyzed the antigen-specific (Gag, Nef, Rev, and Tat) IgM, IgG, and IgA humoral responses during the first 200 days of SIVmac251 infection in cynomolgus macaques. These responses were tested for correlation with the CD4(+) T-cell-related hematologic parameters and viral load throughout the course of the study (acute and chronic infection, during and after antiretroviral therapy). Strong inverse correlations were observed between the percentage of CD4(+) T cells at almost every timepoint of the study and the levels of IgM (but not IgG and IgA) against Gag, Nef, and Rev (but not Tat) measured after, but not during, the primary peak of IgM response. Significant levels of persistent antigen-specific IgMs may reflect the prevalence of mature plasma cells that have not undergone immunoglobulin class switching, possibly due to defects in helper T-cell function. Strong correlations were observed between the preinfection CD4(+) T-cell count or CD4/CD8 ratio and the same parameters measured throughout the study, suggesting the importance of preinfection immune status as a determinant of disease progression. The negative correlations between the post-acute-phase IgM levels and the percentage of CD4(+) T cells at later times during the study suggest the potential prognostic value of this measurement.

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection

“…Thus it is possible that a normal early IgM response in LASV infections is followed by an impaired T helper cell response with sustained IgM production and eventual maturity of the producing B cell subset into an IgM+ B cell memory population. The role of IgM and T-helper lymphocytes have been studied in controlled cynomolgus macaque models of SIV infection [36]. These studies noted a strong inverse correlation of the immunoglobulin and CD4+ T helper cell counts after the primary peak of IgM response, reflecting the prevalence of mature plasma cells that have not undergone class switching.…”

HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits

“…In addition, HIV-1 elicits robust virus-specific IgG responses. While IgG to viral envelope (Env) glycoproteins remains sustained throughout the disease, IgG to group antigen (Gag) and other viral proteins progressively declines19,20. This decline involves especially the IgG2 subclass, which is involved in antiviral defense, whereas IgG1 and IgG3 subclasses are less affected21.…”

Impact of Antiretroviral Treatment on Gene Expression in Peripheral Blood Mononuclear Cells from SIVmac251–Infected Macaques

“…Several mechanisms have been proposed to explain the loss of CD4 + T cells, including apoptosis, disruption of the production and turnover of these cells, changes in their distribution, and alterations in their function [13][14][15][16][17][18]. Assessment of the level of virus antigen-specific IgM in macaques immediately after peak viremia in SIVmac251 infection elucidates defects in CD4 + Th function that reflect impairment of the immune system, which worsens in chronic infection and is predictive of disease progression [4,19].…”