Global changes in the amount of lymphoid tissue have not been studied in the settings of acute, chronic progressive (CP) or long-term non-progressive (LTNP) SIV infection. A better understanding of changes in the total body immune system, especially in those organs capable of expanding or contracting in size, e.g. lymph nodes, may advance our knowledge of SIV pathogenesis.
Uninfected (U, n=10) or SIV (mac251 or mac239)-infected (n=10) rhesus macaques were studied with in vivo CD4 pool SPECT imaging using 99mTc- F(ab΄)2-CD4R1, and volumetric imaging with Computed-Tomography (CT). Only animals with no evidence of immunogenicity to the radiotracer were included. In the cross-sectional analyses, the first scan after 5 months of untreated infection was used. 3 animals were also imaged longitudinally in acute and chronic phase. CD4 pool in the clusters of axillary lymph-nodes (AxLns) was quantified as maximum Standardized-Uptake-Value (SUVmax) of the anti-CD4 probe. The volume of these AxLn (LN-size-Max) were determined from the co-registered CT images.
Five of the SIV infected animals showed features of LTNPs with CD4 T cell count >600 during the entire period of untreated infection (median nadir:743 cells/µl; median SIV RNA set-point:3,760 copies/ml. 4/5 had a protective haplotype). The remaining five showed features of CP with CD4 T counts <500 (median nadir:177 cells/µl; median SIV-RNA of 140,000 copies/ml, 1/5 had a protective haplotype). The SUVmax of the AxLns and the spleen was positively correlated with the peripheral blood CD4 T cell count (r, AxLn = 0.51 (P=0.01); Spleen = 0.74 (P<0.001)). In addition, a positive correlation was observed between the SUVmax and the LN-size-Max (r=0.42, P=0.03). AxLns were larger in the LTNP group compared to the U (P<0.001) or CP groups (P<0.05). No statistically significant differences were noted between the U and CP groups. In the longitudinal study, splenic CD4-pools decreased in all 3 animals in acute phase concomitant with paradoxical increases in the AxLn CD4 pool as well as increases in the volume of AxLns. During the chronic phase of infection, the size of AxLns was reduced in 2 animals (with CP features) but not in the third animal (with LTNP features, B017+).
SPECT/CT imaging during acute and chronic SIV infection highlighted an unexpected association between the size of lymph nodes and the CD4 pool, that may suggest a novel correlate of non-progressive SIV infection.