Early proliferation of CCR5(+) CD38(+++) antigen-specific CD4(+) Th1 effector cells during primary HIV-1 infection.

Abstract

We investigated whether HIV-1 antigen-specific CD4(+) T cells expressed the viral coreceptor CCR5 during primary HIV-1 infection (PHI). In the peripheral blood of subjects with very early PHI (< 22 days after onset of symptoms), there was a 10- to 20-fold increase in the proportion of highly activated (CD38(+++)) and proliferating (Ki-67(+)) CD4(+) T cells that expressed CCR5(+), and were mostly T-cell intracellular antigen-1 (TIA-1)(+) perforin(+) granzyme B(+). Inthe same patient samples, CD4(+) T cells producing interferon (IFN)-gamma in response to HIV group-specific antigen (Gag) peptides were readily detected (median, 0.58%) by intracellular cytokine assay-these cells were again predominantly CD38(+++), Ki-67(+), and TIA-(++), as well as Bcl-2(low). On average, 20% of the Gag-specific CD4(+) T cells also expressed interleukin-2 (IL-2) and were CD127 (IL-7R)(+). Taken together, these results suggest that Gag-specific T-helper 1 (Th1) effector cells express CCR5 during the primary response and may include precursors of long-term self-renewing memory cells. However, in PHI subjects with later presentation, antigen-specific CD4(+) T cells could not be readily detected (median, 0.08%), coinciding with a 5-fold lower level of the CCR5(+)CD38(+++) CD4(+) T cells. These results suggest that the antiviral response to HIV-1 infection includes highly activated CCR5(+)CD4(+) cytotoxic effector cells, which are susceptible to both apoptosis and cytopathic infection with HIV-1, and rapidly decline.

• Authors: John J Zaunders, Mee Ling Munier, Daniel E Kaufmann, Susanna Ip, Pat Grey, Don Smith, Tim Ramacciotti, Dick Quan, Robert Finlayson, John Kaldor, Eric S Rosenberg, Bruce D Walker, David A Cooper, Anthony D Kelleher
• Journal: Blood (Blood) Vol. 106 Issue 5 Pg. 1660-7 (Sep 01 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15905189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Membrane Glycoproteins
• Receptors, CCR5
• ADP-ribosyl Cyclase
• CD38 protein, human
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase (blood, immunology)
• ADP-ribosyl Cyclase 1
• Adult
• Antigens, CD (blood, immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• Cell Proliferation
• HIV Infections (immunology, virology)
• HIV-1 (immunology)
• Humans
• Male
• Membrane Glycoproteins
• Phenotype
• Receptors, CCR5 (blood, immunology)
• Th1 Cells (immunology, metabolism, virology)