841. Peripheral mechanisms of CD4 T cell regeneration in HIV-1 elite controllers
Session: Oral Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011: 9:30 AM
Room: 156ABC
Background: Elite controllers have undetectable levels of HIV-1 replication in the absence of antiretroviral therapy. The majority of the patients also maintain normal CD4 T cells, although effective HIV-1 immune defense in these patients likely requires a significant proportion of their immunological resources. This suggests that specific regenerative immunological mechansims are operational in these patients. 

Methods: Elite controllers, HAART-treated patients, HIV-1 progressors and HIV-1 negative persons (n=15 each) were included into this study. Proportions of naïve, central memory, effector memory and terminally differentiated CD4 T cells were investigated by flow cytometry. Precursor T cell populations were identified by surface staining for protein-tyrosine kinase 7 (PTK7) and CD44 (v. low). Thymic output was quantified by ratios of sjTREC and bTREC levels. 

Results: Relative proportions of naïve T cells in elite controllers were similar to HIV-1 progressors and significantly lower (p<0.01) than in HAART-treated patients and HIV-1 negative individuals. In contrast, levels of central-memory, effector-memory and terminally-differentiated T cells were significantly higher in elite controllers and HIV-1 progressors compared to HIV-1 negative persons and HAART-treated individuals (p<0.01), suggesting that depletion of naïve T cell in elite controllers and progressors was related to their accelerated recruitment to the memory cell pool. Thymic output was similar between elite controllers and HIV-1 negative persons, but significantly lower (p<0.02) in HIV-1 progressors and recipients of HAART. Peripheral precursor T cell populations, such as thymus-dependent PTK7+ T cells and thymus-independent CD44 (v. low) T cells were significantly elevated (p<0.03) in elite controllers compared to all other patient groups. Moreover, homeostatic proliferation of naïve T cells, determined by Ki67 expression, was significantly higher (p<0.02) in elite controllers than in the reference populations. 

Conclusion: Despite severe depletion of naïve CD4 T cells, elite controllers are able to maintain adequate total CD4 T cell counts by expanding peripheral precursor T cells and through peripheral homeostatic proliferation of naive T cells.


Subject Category: H. HIV/AIDS and other retroviruses

Yue Yang, MD1, Jill Beamon1, Katherine Seiss1, Ildiko Toth1, Eric Rosenberg, MD2, Florencia Pereyra, MD1, Xu Yu, MD1 and Mathias Lichterfeld, MD, PhD1, (1)Massachusetts General Hospital, Boston, MA, (2)Pathology, Massachusetts General Hospital, Boston, MA

Disclosures:

Y. Yang, None

J. Beamon, None

K. Seiss, None

I. Toth, None

E. Rosenberg, None

F. Pereyra, None

X. Yu, None

M. Lichterfeld, None

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