The disruption of macaque CD4 + T‐cell repertoires during the early simian immunodeficiency virus infection

Abstract

T-cell receptor (TCR) complementarily determining region 3 (CDR3) spetratyping analysis was employed to assess the ability of an AIDS virus to disrupt CD4 + T-cell repertoires during the primary infection. Rhesus and pig-tailed macaques infected with simian immunodeficiency virus (SIV)mac 251 and SIVsmmFGb, respectively, were evaluated. Following SIV infection, the macaques exhibited an apparent decline of CD4 + peripheral blood lymphocyte (PBL) counts, which was associated with a change in CDR3 profiles from multiple-length distribution to one- or two-length dominance in the selected TCR Vbeta-expressing CD4 + PBL subpopulations. Molecular analysis of the perturbed cell subpopulations suggested that the CD4 + T cells bearing the dominant CDR3 length were clonally expanded. These results indicate that SIV infection can induce a disruption of macaque CD4 + T-cell repertoires during the primary infection. The finding in this study, therefore, suggests that the virus-induced clonal dominance can contribute to the disruption of CD4 + T-cell repertoires.

Interactions between Mycobacterium leprae and simian immunodeficiency virus (SIV) in rhesus monkeys

“…This conclusion is similar to that reached by Zhou et al studying BCG/SIVmac co-infections in rhesus monkeys [24,25]. These investigators observed a transient decrease in viral loads after BCG co-infection in early SIVmac-infected animals that was associated with the development of BCG-driven proliferation of PBL with a TCR CDR3-dependent expansion of Vb-expressing memory CD4+ and CD8+ cell subpopulations [24,25]. In the studies by Zhou et al, the SIVmac/BCG co-infected rhesus monkeys were ini- tially protected from AIDS progression, but eventually experienced a rapid decline in circulating CD4 + T-cells and rapid AIDS progression.…”

“…Thus, there is a correlation between the preservation of these subsets and protection from AIDS progression and death. This conclusion is similar to that reached by Zhou et al studying BCG/SIVmac co-infections in rhesus monkeys [24,25]. These investigators observed a transient decrease in viral loads after BCG co-infection in early SIVmac-infected animals that was associated with the development of BCG-driven proliferation of PBL with a TCR CDR3-dependent expansion of Vb-expressing memory CD4+ and CD8+ cell subpopulations [24,25].…”

“…The study reported herein together with the studies of Zhou et al [24,25], Chen et al [4] and Croix et al [5] provide a powerful argument that there can be a bi-directional interaction between AIDS viruses and mycobacterial diseases. Depending on the relative timing of the two infections, the strain of virus, the identity of the mycobacteria and the doses and routes of the inoculations, a variety of clinical outcomes can be induced.…”

“…In the studies by Zhou et al, the SIVmac/BCG co-infected rhesus monkeys were ini- tially protected from AIDS progression, but eventually experienced a rapid decline in circulating CD4 + T-cells and rapid AIDS progression. Those co-infected rhesus monkeys often developed a progressive pathologic tuberculosis-like infection [24,25]. Chen et al also reported that SIV/BCG co-infection results in a fatal tuberculosis-like systemic infection in rhesus monkeys [4].…”

“…In another recent study by Croix et al, rhesus monkeys infected with SIV B670 followed by BCG inoculation experienced a viremic burst within 2 weeks after BCG which returned to the previous set point by week 8 [5]. Unlike the Zhou et al [24,25] and Chen et al [4] studies, the majority of the SIV/BCG co-infected monkeys in the Croix et al study failed to develop progressive tuberculosis-like pathologic BCG infections [5]. This difference may be related to differences in the routes of BCG inoculation.…”