AEGiS-15IAC: Role for interleukin-7 in maintenance of T cell homeostasis during SIV infection of a monkey species that does not progress to simian AIDS.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Role for interleukin-7 in maintenance of T cell homeostasis during SIV infection of a monkey species that does not progress to simian AIDS.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1443)

Muthukumar A, Zhou D, Milush J, Paiardini M, Barry A, McClure H, Staprans S, Feinberg M, Silvestri G, Sodora DL
University of Texas Southwestern Medical Center, Dallas, United States

BACKGROUND: The infection of the natural host species, sooty mangabeys, with simian immunodeficiency virus (SIVsmm) is characterized by high viral loads and the absence of simian AIDS. In contrast, cross-species transmission of this virus to rhesus macaques (SIVmac) results in CD4 depletion and simian AIDS. Our goal is to assess the ability of SIVsmm infected mangabeys to homeostatically regulate CD4+ T cell levels during the acute phase of the infection, and to compare the SIVsmm-infected mangabeys with pathogenic SIV infections.

METHODS: The SIVsmm infection of six mangabeys was established through direct plasma inoculation, permitting the unique opportunity to monitor the earliest events post-infection. The impact that the SIVsmm infection has on T-cell homeostasis (levels, proliferation, anti-apoptotic factors) during the first 40 weeks post-infection was assessed.

RESULTS: Our results indicate an immediate (weeks 2-4) decline in peripheral blood CD4 levels (reduced 400-1200 CD4+ T-cells/ul) in all six SIVsmm inoculated mangabeys. This CD4 decline correlated with an early significant increase (p<0.05) in the level of plasma IL-7 (weeks 2-4), a cytokine involved in the regulation of T-cell homeostasis. The increased IL-7 levels were followed by an increase in the levels of T cell proliferation (Ki67 in CD4+ and CD8+ T cells) and a stabilization in CD4+ numbers. In contrast, during pathogenic infection of SIV in macaques, elevation of IL-7 levels occurs at later timepoints (after 20 weeks post-infection) and is generally not accompanied by stabilization of CD4+ T-cell numbers.

CONCLUSIONS: These findings suggest that in SIV infected mangabeys, a decline in CD4 T cells results in a homeostatic increase in IL-7 levels during very early times post-infection. The ability of SIV+ mangabeys to homeostatically respond (increase IL-7 levels) early after infection may be a critical component for inhibiting progression to simian AIDS in this species.

Keywords: AEGIS, Simian Acquired Immunodeficiency Syndrome, SIV, Cercocebus atys, Interleukin-7, Cercocebus, CD4-Positive T-Lymphocytes, Macaca mulatta, T-Lymphocytes, Lymphocyte Activation, Antigens, CD4, Infection, Communicable Diseases, Macaca, Cytokines, Viral Load, Animal, immunology

040711
ThOrA1443