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Journal of Virology, August 1999, p. 6661-6669, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activated Memory CD4+ T Helper Cells Repopulate the Intestine Early following Antiretroviral Therapy of Simian Immunodeficiency Virus-Infected Rhesus Macaques but Exhibit a Decreased Potential To Produce Interleukin-2

Joseph J. Mattapallil,1 Zeljka Smit-McBride,1 Peter Dailey,2 and Satya Dandekar1,*

Division of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of California, Davis, Davis,1 and Chiron Corporation, Emeryville,2 California

Received 16 March 1999/Accepted 29 April 1999

Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we performed a longitudinal study to determine the effect of antiretroviral therapy on the phenotype and functional potential of CD4+ T cells repopulating intestinal mucosa in human immunodeficiency virus infection. Severe depletion of CD4+ and CD4+ CD8+ T cells occurred in the intestinal mucosa during primary SIV infection. The majority of these cells were of activated memory phenotype. Phosphonate 9-[2-(phosphomethoxypropyl]adenine (PMPA) treatment led to a moderate suppression of intestinal viral loads and repopulation of intestinal mucosa by predominantly activated memory CD4+ T-helper cells. This repopulation was independent of the level of viral suppression. Compared to preinfection values, the frequency of naive CD4+ T cells increased following PMPA therapy, suggesting that new CD4+ T cells were repopulating the intestinal mucosa. Repopulation by CD4+ CD8+ T cells was not observed in either jejunum or colon lamina propria. The majority of CD4+ T cells repopulating the intestinal mucosa following PMPA therapy were CD29hi and CD11ahi. A subset of repopulating intestinal CD4+ T cells expressed Ki-67 antigen, indicating that local proliferation may play a role in the repopulation process. Although the majority of repopulating CD4+ T cells in the intestinal mucosa were functionally capable of providing B- and T-cell help, as evidenced by their expression of CD28, these CD4+ T cells were found to have a reduced capacity to produce interleukin-2 (IL-2) compared to the potential of CD4+ T cells prior to SIV infection. Persistent viral infection may play a role in suppressing the potential of repopulating CD4+ T cells to produce IL-2. Hence, successful antiretroviral therapy should aim at complete suppression of viral loads in mucosal lymphoid tissues, such as intestinal mucosa.

* Corresponding author. Mailing address: Division of Infectious Diseases, Room 3143, Tupper Hall, School of Medicine, University of California, Davis, Davis, CA 95616. Phone: (530) 752-3542. Fax: (530) 752-8692. E-mail: sdandekar{at}ucdavis.edu.

Journal of Virology, August 1999, p. 6661-6669, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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