The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4 + memory T cell (T M) homeostasis. CD4+ naive T cells (T N) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4 + T N in SIV pathogenesis using rhesus macaques (RM s) selectively and permanently depleted of CD4 + T N before SIV infection. CD4 + T N-depleted and CD4 + T N-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4 + T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4 + T M recovery, only sham-treated RMs reconstituted CD4 + T N. CD4 + T N-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4 + T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8 + T cell responses. However, CD4 + T N-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4 + T N deficiency had no significant effect on CD4 + T M homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4 + T N compartment is dispensable for CD4 + T M homeostasis in progressive SIV infection, and they confirm that CD4 + T M comprise a homeostatically independent compartment that is intrinsically capable of self-renewal.
ASJC Scopus subject areas
- Immunology and Allergy